Tokushima University / Educator and Researcher Directory --- Yao, Chenjuan

Personal Web Page

https://researchmap.jp/read0088378 (researchmap)

Field of Study

○	Dentistry

Subject of Study

○

Book / Paper

Book:

1.	Tetsuya Akamatsu, Chenjuan Yao and Kazuo Hosoi : Methods for animal tissue culture and techniques to prevent cell death, growth defect, and cell mutation, Technical Information Institute Co., Ltd., Apr. 2014. (Keyword) salivary gland / tissue culture / induction of differentiation
2.	Chenjuan Yao and Chenjuan Yao : Handbook of proteolytic enzymes, --- "Mouse kallikreins mK13 and mK26" ---, Elsevier (Academic press imprint), Oxford, 2013.
3.	Kazuo Hosoi, Chenjuan Yao and others : Handbook of proteolytic enzymes, 3rd Edition, Elsevier Scientific Publishing Company, Amsterdam, 2011. (Keyword) kallikreins / mK13 / mK26 / mouse

Academic Paper (Judged Full Paper):

1.	Yanhong Chen, Yingqi Liu, Yanli Li, Chenjuan Yao, Jianhua Qu, Juan Tang, Gang Chen and Yu Han : Acute exposure to polystyrene nanoplastics induces unfolded protein response and global protein ubiquitination in lungs of mice., Ecotoxicology and Environmental Safety, Vol.280, 116580, 2024. (Summary) Inhaling microplastics (MPs) and nanoplastics (NPs) in the air can damage lung function. Xenobiotics in the body can cause endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) activation alleviates ER stress. Degradation of unfolded or misfolded proteins is an important pathway for recovering cellular homeostasis. The UPR and protein degradation induced by MPs/NPs in lung tissues are not well understood. Here, we investigated the UPR and protein ubiquitination in the lungs of mice exposed to polystyrene (PS)-NPs and their possible molecular mechanisms leading to protein ubiquitination. Mice were intratracheally administered with 5.6, 17, and 51 mg/kg PS-NPs once for 24 h. Exposure to PS-NPs elevated protein ubiquitination in the lungs of mice in a dose-dependent manner. PS-NPs activated three branches of UPR including inositol-requiring protein 1α (IRE1α), eukaryotic translation initiator factor 2α (eIF2α), and activating transcription factor 6α (ATF6α) in the lungs of mice. However, activated IRE1α did not trigger X-box binding protein 1 (XBP1) mRNA splicing. Exposure to PS-NPs induced an increase in the levels of E3 ubiquitin ligase hydroxymethyl glutaryl-coenzyme A reductase degradation protein 1 (HRD1) and carboxy terminus of Hsc70 interacting protein (CHIP) in the lungs of mice and BEAS-2B cells. ATF6α siRNA inhibited the levels of HRD1 and CHIP proteins induced by PS-NPs in BEAS-2B cells. These results suggest that ATF6α plays a critical role in increasing ubiquitination of unfolded or misfolded proteins by alleviating PS-NPs induced ER stress through UPR to achieve ER homeostasis in the lungs of mice. (Keyword) Animals / Ubiquitination / Mice / Unfolded Protein Response / Lung / Polystyrenes / Microplastics / male / Endoplasmic Reticulum Stress / nanoparticles / Mice, Inbred C57BL (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ecoenv.2024.116580 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38865938 ● Search Scopus @ Elsevier (PMID): 38865938 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ecoenv.2024.116580 (DOI: 10.1016/j.ecoenv.2024.116580, PubMed: 38865938)
2.	Yanli Li, Yingqi Liu, Yanhong Chen, Chenjuan Yao, Shali Yu, Jianhua Qu, Gang Chen and Haiyan Wei : Combined effects of polystyrene nanoplastics and lipopolysaccharide on testosterone biosynthesis and inflammation in mouse testis., Ecotoxicology and Environmental Safety, Vol.273, 116180, 2024. (Summary) Microplastics (MPs)/nanoplastics (NPs), as a source and vector of pathogenic bacteria, are widely distributed in the natural environments. Here, we investigated the combined effects of polystyrene NPs (PS-NPs) and lipopolysaccharides (LPS) on testicular function in mice for the first time. 24 male mice were randomly assigned into 4 groups, control, PS-NPs, LPS, and PS-NPs + LPS, respectively. Histological alterations of the testes were observed in mice exposed to PS-NPs, LPS or PS-NPs + LPS. Total sperm count, the levels of testosterone in plasma and testes, the expression levels of steroidogenic acute regulatory (StAR) decreased more remarkable in testes of mice treated with PS-NPs and LPS than the treatment with LPS or PS-NPs alone. Compared with PS-NPs treatment, LPS treatment induced more sever inflammatory response in testes of mice. Moreover, PS-NPs combined with LPS treatment increased the expression of these inflammatory factors more significantly than LPS treatment alone. In addition, PS-NPs or LPS treatment induced oxidative stress in testes of mice, but their combined effect is not significantly different from LPS treatment alone. These results suggest that PS-NPs exacerbate LPS-induced testicular dysfunction. Our results provide new evidence for the threats to male reproductive function induced by both NPs and bacterial infection in human health. (Keyword) Humans / Animals / male / Mice / Testis / Lipopolysaccharides / Microplastics / plastics / Polystyrenes / Semen / inflammation / Testosterone / nanoparticles (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ecoenv.2024.116180 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38458071 ● Summary page in Scopus @ Elsevier: 2-s2.0-85187011326 (DOI: 10.1016/j.ecoenv.2024.116180, PubMed: 38458071, Elsevier: Scopus)
3.	Shintaroh Kusunoki, Takako Fukuda, Saori Maeda, Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu and Hiroshi Yoshimura : Relationships between feeding behaviors and emotions: An electroencephalogram (EEG) frequency analysis study, The Journal of Physiological Sciences, Vol.73, No.1, 2, 2023. (Summary) Feeding behaviors may be easily affected by emotions, both being based on brain activity; however, the relationships between them have not been explicitly defined. In this study, we investigated how emotional environments modulate subjective feelings, brain activity, and feeding behaviors. Electroencephalogram (EEG) recordings were obtained from healthy participants in conditions of virtual comfortable space (CS) and uncomfortable space (UCS) while eating chocolate, and the times required for eating it were measured. We found that the more participants tended to feel comfortable under the CS, the more it took time to eat in the UCS. However, the EEG emergence patterns in the two virtual spaces varied across the individuals. Upon focusing on the theta and low-beta bands, the strength of the mental condition and eating times were found to be guided by these frequency bands. The results determined that the theta and low-beta bands are likely important and relevant waves for feeding behaviors under emotional circumstances, following alterations in mental conditions. (Keyword) Feeding behavior / Emotion / electroencephalogram / Fast Fourier Transform / Virtual space (Tokushima University Institutional Repository) ● Metadata: 118602 (Link to Publication Site) ● Publication site (DOI): 10.1186/s12576-022-00858-w (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36869303 ● Search Scopus @ Elsevier (PMID): 36869303 ● Search Scopus @ Elsevier (DOI): 10.1186/s12576-022-00858-w (Tokushima University Institutional Repository: 118602, DOI: 10.1186/s12576-022-00858-w, PubMed: 36869303)
4.	Jing Tang, Chenjuan Yao, Yingqi Liu, Jiaming Yuan, Li Wu, Kazuo Hosoi, Shali Yu, Chunyan Huang, Haiyan Wei and Gang Chen : Arsenic trioxide induces expression of BCL-2 expression via NF-κB and p38 MAPK signaling pathways in BEAS-2B cells during apoptosis, Ecotoxicology and Environmental Safety, Vol.222, 112531, 2021. (Summary) Inorganic arsenic compounds are environmental toxicants that are widely distributed in air, water, and food. B-cell lymphoma 2 (BCL-2) is an oncogene having anti-apoptotic function. In this study, we clarify that BCL-2, as a pro-apoptotic factor, participates in AsO-induced apoptosis in BEAS-2B cells. Specifically, AsO stimulated the expression of BCL-2 mRNA and protein in a dose-dependent manner which was highly accumulated in the nucleus of BEAS-2B cell together with chromatin condensation and DNA fragmentation during apoptosis. Mechanistically, the process described above is mediated through the NF-κB and p38 MAPK signaling pathways, which can be abated by corresponding inhibitors, such as BAY11-7082 and SB203580, respectively. Additionally, BAY11-7082, actinomycin D, and cycloheximide have inhibitory effects on AsO-induced expression of BCL-2 mRNA and protein, and restore the cell viability of BEAS-2B cells. Suppression of BCL-2 protein activation by ABT-199 also restored viability of BEAS-2B cell in AsO-induced apoptosis. Furthermore, AsO increased the level of BCL-2 phosphorylation. These results suggest that in BEAS-2B cells, AsO-induced apoptosis is mainly dominated by BCL-2 upregulation, nuclear localization and phosphorylation. The study presented here provides a novel insight into the molecular mechanism of BCL-2-induced apoptosis. (Keyword) apoptosis / Arsenic Trioxide / Arsenicals / NF-kappa B / Oxides / Proto-Oncogene Proteins c-bcl-2 / p38 Mitogen-Activated Protein Kinases (Tokushima University Institutional Repository) ● Metadata: 116727 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ecoenv.2021.112531 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34303041 ● Summary page in Scopus @ Elsevier: 2-s2.0-85110571403 (Tokushima University Institutional Repository: 116727, DOI: 10.1016/j.ecoenv.2021.112531, PubMed: 34303041, Elsevier: Scopus)
5.	Yingqi Liu, Jing Tang, Jiaming Yuan, Chenjuan Yao, Kazuo Hosoi, Yu Han, Shali Yu, Haiyan Wei and Gang Chen : Arsenite-induced downregulation of occludin in mouse lungs and BEAS-2B cells via the ROS/ERK/ELK1/MLCK and ROS/p38 MAPK signaling pathways., Toxicology Letters, Vol.332, 146-154, 2020. (Summary) inhibits occludin expression in vivo and in vitro at least partially via the ROS/ERK/ELK1/MLCK and ROS/p38 MAPK signaling pathways. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.toxlet.2020.07.010 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32683294 ● Summary page in Scopus @ Elsevier: 2-s2.0-85087966931 (DOI: 10.1016/j.toxlet.2020.07.010, PubMed: 32683294, Elsevier: Scopus)
6.	Yingqi Liu, Haiyan Wei, Jing Tang, Jiaming Yuan, Mingmin Wu, Chenjuan Yao, Kazuo Hosoi, Shali Yu, Xinyuan Zhao, Yu Han and Gang Chen : Dysfunction of pulmonary epithelial tight junction induced by silicon dioxide nanoparticles via the ROS/ERK pathway and protein degradation., Chemosphere, Vol.255, 126954, 2020. (Summary) Silica nanoparticles (SiNPs) are one of the most widely used types of nanoparticles across many industrial sectors, and are known to be present in the air year-round. In this study, we aimed to evaluate the potential adverse effects of SiNP exposure on pulmonary epithelial tight junctions, which serve as a critical barrier between the respiratory system and the circulatory system. In vivo studies confirmed that SiNPs decreased the protein expression levels of zonula occludens 1 (ZO-1), zonula occludens 2 (ZO-2), and occludin in the lungs of C57BL/6 mice. In vitro studies showed that SiNPs not only decreased the mRNA and protein expression of ZO-1 and ZO-2, but also decreased the protein expression of occludin in human bronchial epithelial (BEAS-2B) cells. In addition, SiNP exposure increased reactive oxygen species (ROS) production and activated extracellular regulated protein kinases (ERKs) and c-Jun N-terminal kinase (JNK). The inhibition of ROS and ERKs effectively protected the SiNP-induced downregulation of ZO-1 mRNA and protein expression, but had no effect on ZO-2 or occludin expression. SiNP-induced matrix metalloproteinase 9 (MMP9) protein expression appeared to be involved in occludin proteolytic degradation, in addition to SiNP-induced direct occludin protein degradation. The present study suggests that SiNPs disturb pulmonary epithelial tight junction structure and function via the ROS/ERK pathway and protein degradation. (Keyword) Animals / Bronchi / Down-Regulation / Humans / JNK Mitogen-Activated Protein Kinases / Lung / MAP Kinase Signaling System / Mice / Mice, Inbred C57BL / nanoparticles / Occludin / Phosphoproteins / Proteolysis / reactive oxygen species / Silicon Dioxide / Tight Junctions / Zonula Occludens-1 Protein (Link to Publication Site) ● Publication site (DOI): 10.1016/j.chemosphere.2020.126954 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32387908 ● Summary page in Scopus @ Elsevier: 2-s2.0-85084223128 (DOI: 10.1016/j.chemosphere.2020.126954, PubMed: 32387908, Elsevier: Scopus)
7.	Xiaoke Wang, Piaoyu Zhu, Shenya Xu, Yuting Liu, Yang Jin, Shali Yu, Haiyan Wei, Jinlong Li, Qinglin Zhang, Takahiro Hasegawa, Chenjuan Yao, Hiroshi Yoshimura, Qiyun Wu and Xinyuan Zhao : Antimony, a novel nerve poison, triggers neuronal autophagic death via reactive oxygen species-mediated inhibition of the protein kinase B/mammalian target of rapamycin pathway., The International Journal of Biochemistry & Cell Biology, Vol.114, 105561, 2019. (Summary) Antimony (Sb), a naturally occurring metal present in air and drinking water, has been found in the human brain, and there is evidence of its toxic effects on neurobehavioral perturbations, suggesting that Sb is a potential nerve poison. Here, we provide the first study on the molecular mechanism underlying Sb-associated neurotoxicity. Mice exposed to antimony potassium tartrate hydrate showed significantly increased neuronal apoptosis. In vitro, Sb triggered apoptosis in PC12 cells in a dose-dependent manner. Mechanically, Sb triggered autophagy as indicated by increased expression of microtubule-associated protein 1 light chain 3-II (LC3-II) and accumulation of green fluorescent protein-tagged LC3 dots. Moreover, Sb enhanced autophagic flux and sequestosome 1 (p62) degradation. Subsequent analyses showed that Sb treatment decreased phosphorylation of protein kinase B (Akt) as well as the mammalian target of rapamycin (mTOR), while an Akt activator protected PC12 cells from autophagy. Moreover, the antioxidant N-acetylcysteine attenuated Sb-induced Akt/mTOR inhibition and decreased autophagy and apoptosis, with autophagy inhibition also playing a cytoprotective role. In vivo, mice treated with Sb showed higher expression of LC3-II and p62 in the brain, consistent with the in vitro results. In summary, Sb induced autophagic cell death through reactive oxygen species-mediated inhibition of the Akt/mTOR pathway. (Keyword) Animals / Antimony / Autophagic Cell Death / Mice / Nerve Agents / Neurons / PC12 Cells / Proto-Oncogene Proteins c-akt / Rats / Reactive Oxygen Species / TOR Serine-Threonine Kinases (Link to Publication Site) ● Publication site (DOI): 10.1016/j.biocel.2019.105561 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31228582 ● Search Scopus @ Elsevier (PMID): 31228582 ● Search Scopus @ Elsevier (DOI): 10.1016/j.biocel.2019.105561 (DOI: 10.1016/j.biocel.2019.105561, PubMed: 31228582)
8.	Xinyuan Zhao, Yang Jin, Lijia Yang, Zhengxing Hou, Yingqi Liu, Tianyu Sun, Jiaxin Pei, Jinlong Li, Chenjuan Yao, Xiaoke Wang and Gang Chen : Promotion of SIRT1 protein degradation and lower SIRT1 gene expression via reactive oxygen species is involved in Sb-induced apoptosis in BEAS-2b cells., Toxicology Letters, Vol.296, No.504, 73-81, 2018. (Summary) Antimony (Sb) has been reported to lead to pulmonary damage, but the underlying mechanism remains unclear. Accumulating evidence indicates that silent mating type information regulation 2 homolog 1 (SIRT1), an NAD-dependent deacetylase, mediates stimuli-induced cellular apoptosis. Here, we investigated whether SIRT1 plays a role in Sb-triggered apoptosis in human bronchial epithelial cells (BEAS-2b). First, we showed that Sb initiated apoptosis. Furthermore, the expression of SIRT1 was markedly downregulated by Sb treatment, while overexpression of SIRT1 through resveratrol treatment or transfection with SIRT1-Flag plasmid attenuated the Sb-induced apoptosis. Accelerated degradation of SIRT1 protein and lower SIRT1 gene expression contributed to low expression of SIRT1. In addition, Sb activated the ERK and JNK pathways; however, inhibition of ERK rather than JNK rescued SIRT1 suppression. Subsequent analyses demonstrated that antioxidant N-acetylcysteine (NAC) attenuated SIRT1 repression, increased SIRT1 mRNA levels and decreased SIRT1 protein degradation in Sb-treated cells. In addition, NAC also inhibited JNK and ERK activation by Sb exposure. These data suggest that reactive oxygen species-dependent SIRT1 suppression mediates Sb-stimulated cell apoptosis in BEAS-2b cells via lower SIRT1 gene expression and protein stability. (Keyword) Acetylcysteine / Animals / Antimony / Antioxidants / Apoptosis / Cell Line / Gene Expression / MAP Kinase Signaling System / Plasmids / Rats / Reactive Oxygen Species / Sincalide / Sirtuin 1 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.toxlet.2018.07.047 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30055241 ● Search Scopus @ Elsevier (PMID): 30055241 ● Search Scopus @ Elsevier (DOI): 10.1016/j.toxlet.2018.07.047 (DOI: 10.1016/j.toxlet.2018.07.047, PubMed: 30055241)
9.	Haiyan Wei, Qiaoyun Hu, Junxia Wu, Chenjuan Yao, Lingfei Xu, Fengjun Xing, Xinyuan Zhao, Shali Yu, Xiaoke Wang and Gang Chen : Molecular mechanism of the increased tissue uptake of trivalent inorganic arsenic in mice with type 1 diabetes mellitus., Biochemical and Biophysical Research Communications, Vol.504, No.2, 393-399, 2018. (Summary) Arsenic is associated with several adverse health outcomes, and people with diabetes may be more susceptible to arsenic. In this study, we found that arsenic levels in some tissues such as liver, kidney, and heart but not lung of type 1 diabetes mellitus (T1DM) mice were higher than in those of normal mice after a single oral dose of arsenic trioxide for 2 h. However, little is known about the molecular mechanism of the increased tissue uptake of trivalent inorganic arsenic in mice with T1DM. This study aimed to investigate the expression of the mammalian arsenic transporters aquaglyceroporins (AQPs) and glucose transporter 1 (GLUT1) in T1DM mice and compare them with those in normal mice. Results showed that the levels of AQP9 and GLUT1 mRNA and protein were higher in T1DM mouse liver than in the normal one. The levels of AQP7 mRNA and protein were higher in T1DM mouse kidney. In the heart, we observed that the levels of AQP7 and GLUT1 mRNA and protein were higher in T1DM mice, but the levels of AQP9 mRNA and protein in the lung had no significant difference between both mice. These results suggested that T1DM may increase the expression of transporters of trivalent inorganic arsenic and thus increase the arsenic uptake in specific tissues. (Keyword) Animals / Aquaporins / Arsenic / Arsenic Trioxide / Arsenites / Biological Transport / Blood Glucose / Body Weight / Diabetes Mellitus, Type 1 / Glucose Transporter Type 1 / Inorganic Chemicals / Kidney / Liver / Male / Mice / Mice, Inbred ICR / RNA, Messenger / Tissue Distribution (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2018.06.029 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29890131 ● Search Scopus @ Elsevier (PMID): 29890131 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2018.06.029 (DOI: 10.1016/j.bbrc.2018.06.029, PubMed: 29890131)
10.	Hiroshi Yoshimura, Sugai Tokio, Kato Nobuo, Tominaga Takashi, Tominaga Yoko, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : Interplay between non-NMDA and NMDA receptor activation during oscillatory wave propagation: Analyses of caffeine-induced oscillations in the visual cortex of rats, Neural Networks, Vol.79, 141-149, 2016. (Summary) Generation and propagation of oscillatory activities in cortical networks are important features of the brain. However, many issues related to oscillatory phenomena are unclear. We previously reported neocortical oscillation following caffeine treatment of rat brain slices. Input to the primary visual cortex (Oc1) generates N-methyl-d-aspartate (NMDA) receptor-dependent oscillations, and we proposed that the oscillatory signals originate in the secondary visual cortex (Oc2). Because non-NMDA and NMDA receptors cooperate in synaptic transmission, non-NMDA receptors may also play an important role in oscillatory activities. Here we investigated how non-NMDA receptor activities contribute to NMDA receptor-dependent oscillations by using optical recording methods. After induction of stable oscillations with caffeine application, blockade of NMDA receptors abolished the late stable oscillatory phase, but elicited 'hidden' non-NMDA receptor-dependent oscillation during the early depolarizing phase. An interesting finding is that the origin of the non-NMDA receptor-dependent oscillation moved from the Oc1, during the early phase, toward the origin of the NMDA receptor-dependent oscillation that is fixed in the Oc2. In addition, the frequency of the non-NMDA receptor-dependent oscillation was higher than that of the NMDA receptor-dependent oscillation. Thus, in one course of spatiotemporal oscillatory activities, the relative balance in receptor activities between non-NMDA and NMDA receptors gradually changes, and this may be due to the different kinetics of the two receptor types. These results suggest that interplay between the two receptor types in the areas of Oc1 and Oc2 may play an important role in oscillatory signal communication. (Keyword) neural oscillation / non-NMDA receptor / NMDA-receptors / caffeine / rat (Link to Publication Site) ● Publication site (DOI): 10.1016/j.neunet.2016.03.012 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27136667 ● Search Scopus @ Elsevier (PMID): 27136667 ● Search Scopus @ Elsevier (DOI): 10.1016/j.neunet.2016.03.012 (DOI: 10.1016/j.neunet.2016.03.012, PubMed: 27136667)
11.	Hiroshi Yoshimura, 川邊真道, 須貝外喜夫, 加藤伸郎, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : Influences of oral impairment on neural oscilltion and wave propagation in the neocortex of rats, Neuroscience Research Suppl, Vol.Suppl, 2015.
12.	Javkhlan Purevjav, Xu Guangfei, Chen Gang, Chenjuan Yao, Yuka Hiroshima, Hiroshi Yoshimura, Toshihiko Nagata and Kazuo Hosoi : Expression and LPS-Induced Elevation of Nod2 and Calprotectin in the Submandibular Gland of Wild-Type and TLR4-Knockout Male Mice, Journal of Research and Practice in Dentistry, Vol.2015, No.290259, 2015. (Link to Publication Site) ● Publication site (DOI): 10.5171/2015.290259 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.5171/2015.290259 (DOI: 10.5171/2015.290259)
13.	Gang Chen, Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu, Hiroshi Yoshimura and Kazuo Hosoi : Effects of isoproterenol on aquaporin 5 levels in the parotid gland of mice in vivo., American Journal of Physiology, Endocrinology and Metabolism, Vol.306, No.1, E100-E108, 2014. (Summary) In the membrane fraction of mouse parotid gland (PG), the protein level of aquaporin 5 (AQP5), a member of the water channel family, was increased by injection (ip) of isoproterenol (IPR), a β-adrenergic agonist, at 1 h, and stayed at high levels until 6 h; this change occurred simultaneously as amylase secretion. The AQP5 level then decreased and returned toward the original level at 12-48 h. After IPR injection, the AQP5 mRNA gradually increased and reached a maximum at 24 h. The facts suggest a rapid appearance of AQP5 at plasma membrane by IPR and subsequent degradation/metabolism by activation of proteolytic systems. Pretreatment of animals with two calpain inhibitors, N-Ac-Leu-Leu-methininal (ALLM) and calpeptin, as well as a protein synthesis inhibitor, cycloheximide (CHX), significantly suppressed the IPR-induced AQP5 degradation in the PG membrane fraction; such suppression was not observed by two proteasome inhibitors, MG132 and lactacystin, or the lysosome denaturant chloroquine, although most of these inhibitors increased AQP5 protein levels in unstimulated mice. The AQP5 protein was also degraded by μ-calpain in vitro. Furthermore, we demonstrated that μ-calpain was colocalized with AQP5 in the acinar cells by immunohistochemistry, and its activity in the PG was increased at 6 h after IPR injection. These results suggest that the calpain system was responsible for IPR-induced AQP5 degradation in the parotid gland and that such a system was coupled to the secretory-restoration cycle of amylase in the PG. (Keyword) aquaporin 5 / parotid gland / isoproterenol (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpendo.00317.2013 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24192288 ● Summary page in Scopus @ Elsevier: 2-s2.0-84891527146 (DOI: 10.1152/ajpendo.00317.2013, PubMed: 24192288, Elsevier: Scopus)
14.	Hiroshi Yoshimura, Tokio Sugai, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Nobuo Kato : Age-dependent emergence of caffeine-assisted voltage oscillations in the endopiriform nucleus of rats., Neuroscience Research, Vol.76, No.1-2, 16-21, 2013. (Summary) The gustatory insular cortex (IC) is connected with not only the somatosensory cortex, but also the endopiriform nucleus (EPN). We have previously revealed that low-frequency electrical stimulation to the IC can elicit membrane potential oscillations at a frequency of 8-10 Hz in the somatosensory cortex of rat brain slices under bath-application of caffeine. Using the same procedure, we investigated whether the EPN has the ability to generate oscillations, and whether such oscillations emerge age-dependently. Electrical stimulations were delivered to the IC, and field potentials were recorded from the EPN. In the case of slices made from mature rats, stable field potential oscillations at 8-10 Hz were induced in the EPN after repetitive stimulations. Optical recordings revealed that signals traveled from the IC to the EPN by way of the claustrum. Generation of oscillations was N-methyl-d-aspartate (NMDA) receptor activity-dependent, since oscillatory phases disappeared following application of NMDA receptor antagonist. In slices from immature rats, however, oscillations were not induced. IC stimulation can thus age-dependently elicit membrane potential oscillations in the EPN, and the EPN oscillations were NMDA receptor activity-dependent. These findings suggest that developmental changes in properties of the EPN might contribute to development of information integration, including gustatory information. (Keyword) aging / Animals / Caffeine / Central Nervous System Stimulants / Cerebral Cortex / Electric Stimulation / Membrane Potentials / Organ Culture Techniques / Rats / Rats, Wistar (Link to Publication Site) ● Publication site (DOI): 10.1016/j.neures.2013.02.010 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23517711 ● Summary page in Scopus @ Elsevier: 2-s2.0-84884702568 (DOI: 10.1016/j.neures.2013.02.010, PubMed: 23517711, Elsevier: Scopus)
15.	Nunuk Purwanti, Mileva Ratko Karabasil, Shinsuke Matsuo, Gang Chen, Javkhlan Purevjav, Ahmad Azlina, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Induction of Sca-1 via activation of STAT3 system in the duct cells of the mouse submandibular gland by ligation of the main excretory duct, American Journal of Physiology, Gastrointestinal and Liver Physiology, Vol.301, No.5, G814-G824, 2011. (Summary) To examine the very initial step that takes place immediately after tissue injury and is linked to tissue regeneration, we employed the submandibular gland (SMG), which was injured by ligation of its main excretory duct (MED). Ligation of the MED of the SMG in mice induced the expression of Sca-1, a protein marker of hematopoietic stem cells. In the normal gland, a low level of Sca-1 was expressed, which was localized predominantly in the excretory duct cells. At 1 day after ligation, Sca-1 expression increased prominently in almost all of cells in the duct system, but not in the acinar cells. The level of Sca-1 mRNA had begun to increase at 6 h after ligation and continuously rose thereafter until it reached a plateau, which occurred ∼12 h after ligation. STAT3 phosphorylated at its tyrosine-705 (p-STAT3) in the ligated gland increased immediately after ligation, and it was localized in the nuclei of all duct cells. The results of an EMSA revealed the specific binding of a nuclear extract to the sequence of the γ-interferon activation site (GAS) present in the Sca-1 promoter and confirmed that such binding increased after ligation. Thus the present study suggests that STAT3, having been phosphorylated following MED ligation, was transferred to the nucleus, where it bound to the GAS element in the promoter of Sca-1 gene, resulting in promotion of Sca-1 gene expression. Actual prevention of STAT3 phosphorylation reduced the ligation-induced Sca-1 elevation. (Keyword) Animals / Antigens, Ly / Ligation / Membrane Proteins / Mice / Phosphorylation / Promoter Regions, Genetic / STAT3 Transcription Factor / Salivary Ducts / Submandibular Gland (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpgi.00408.2010 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21868636 ● Search Scopus @ Elsevier (PMID): 21868636 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpgi.00408.2010 (DOI: 10.1152/ajpgi.00408.2010, PubMed: 21868636)
16.	Purevjav Javkhlan, Yuka Hiroshima, Ahmad Azlina, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu, Jun-ichi Kido, Toshihiko Nagata and Kazuo Hosoi : Lipopolysaccharide-mediated induction of calprotectin in the submandibular and parotid glands of mice, Inflammation, Vol.34, No.6, 668-680, 2011. (Summary) S100A8 and S100A9 constitute a heterodimeric protein, calprotectin. The mRNAs of S100A8 and S100A9, being expressed at minimal levels in the submandibular and parotid glands (SMG and PG, respectively) of C3H/HeN mice, were induced strongly and transiently by lipopolysaccharide (LPS). Among the mRNAs of members of the S100 protein family examined, those of S100A8 and S100A9 were specifically induced by LPS in the salivary glands. The induction was assumed to be mediated via toll-like receptor 4 (TLR4), since their elevation was limited in C3H/HeJ mice, a TLR4-mutant strain. These proteins became expressed in the granular convoluted tubular cells and striated duct cells in the SMG, and in both acinar and duct cells in the PG (all in the cytoplasm). The salivary calprotectin level was not increased by LPS treatment, implying that elevated calprotectin was not secreted into the saliva and that they may function in microcellular environment of the salivary gland. (Keyword) Animals / Calgranulin A / Calgranulin B / Leukocyte L1 Antigen Complex / Lipopolysaccharides / Mice / Parotid Gland / RNA, Messenger / Salivary Glands / Submandibular Gland / Transcriptional Activation (Link to Publication Site) ● Publication site (DOI): 10.1007/s10753-010-9277-1 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21125321 ● Search Scopus @ Elsevier (PMID): 21125321 ● Search Scopus @ Elsevier (DOI): 10.1007/s10753-010-9277-1 (DOI: 10.1007/s10753-010-9277-1, PubMed: 21125321)
17.	Takahiro Hasegawa, Ahmad Azlina, Javkhlan Purevjav, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Novel phosphorylation of aquaporin-5 at its threonine 259 through cAMP signaling, American Journal of Physiology, Cell Physiology, Vol.301, No.3, C667-C678, 2011. (Summary) Aquaporin-5 (AQP5), a water channel, plays key roles in salivary secretion. The novel phosphorylation of AQP5 was investigated by using human salivary gland (HSG) cells and mouse salivary glands. In the HSG cells stably transfected with a wild-type mouse AQP5 construct, a protein band immunoreactive with antibody against phosphorylated PKA substrate was detected in the AQP5 immunoprecipitated sample, and its intensity was enhanced by short-term treatment of the cells with 8-bromo-cAMP, forskolin, or phorbol 12-myristate 13-acetate, but not by that with A23187 calcium ionophore. Such enhancement was inhibited in the presence of H-89, a PKA inhibitor. An AQP5 mutant (AQP5-T259A) expressed by transfection of HSG cells was not recognized by anti-phosphorylated PKA substrate antibody, even when the cells were stimulated with the protein kinase activators. Immunoblotting and immunofluorescence studies using a specific antibody detecting AQP5 phosphorylated at its Thr259 demonstrated that AQP5 was rapidly and transiently phosphorylated at the apical membrane of acinar cells in the submandibular and parotid glands after administration of isoproterenol, but not pilocarpine. Furthermore, both AQP5 and AQP5-T259A were constitutively localized at the plasma membrane in HSG cells under the resting and forskolin-stimulated conditions. These results suggest that AQP5 is phosphorylated at its Thr259 by PKA through cAMP, but not Ca(2+), signaling pathways, and that this phosphorylation does not contribute to AQP5 trafficking in the salivary gland cells. (Keyword) Amino Acid Substitution / Animals / Antibodies / Antibody Specificity / Aquaporin 5 / Calcimycin / Cell Line, Tumor / Cell Membrane / Cyclic AMP / Cyclic AMP-Dependent Protein Kinases / Detergents / Forskolin / Humans / Isoproterenol / Isoquinolines / Male / Mice / Mice, Inbred ICR / Parotid Gland / Phosphorylation / Pilocarpine / Protein Kinase Inhibitors / Protein Transport / Salivary Glands / Signal Transduction / Submandibular Gland / Sulfonamides / Tetradecanoylphorbol Acetate / Threonine / Transfection (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpcell.00058.2011 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21633078 ● Search Scopus @ Elsevier (PMID): 21633078 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpcell.00058.2011 (DOI: 10.1152/ajpcell.00058.2011, PubMed: 21633078)
18.	Nunuk Purwanti, Daisuke Tsuji, Ahmad Azlina, Mileva Ratko Karabasil, Purevjav Javkhlan, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu, Kouji Itou and Kazuo Hosoi : Induction of Sca-1 in the duct cells of the mouse submandibular gland by obstruction of the main excretory duct, Journal of Oral Pathology & Medicine, Vol.40, No.8, 651-658, 2011. (Summary) The effect of ligation of the main excretory duct (MED) of the mouse submandibular gland (SMG) on the expression of Sca-1, a stem cell antigen, was examined by Western blotting and immunohistochemistry. By Western blotting, the expression of Sca-1 with a molecular weight of 18 kDa was identified in the normal gland. At 1 day post-ligation, the expression level of Sca-1 was strongly increased in the experimental gland and weakly in the contralateral gland, and such expression in both glands decreased at 6 days. By immunohistochemistry, Sca-1 was detected weakly in the apical membrane of excretory duct (ED) cells of the SMG under the normal condition. By duct ligation, Sca-1 became expressed strongly in most cells of the two major duct systems, i.e., the striated duct (SD) and granular convoluted tubules (GCT), but was not detected in the acinar (Ac) cells. By fluorescence-activated cell sorter (FACS) analysis, the number of side population (SP) cells in this gland was found to be increased by ligation. These results imply that Sca-1-positive cells may have a role in the duct cell proliferation in the regeneration step elicited by MED ligation-induced injury. (Keyword) Animals / Antigens, Ly / Cell Count / Cell Proliferation / Ligation / Male / Membrane Proteins / Mice / Mice, Inbred C57BL / Regeneration / Salivary Ducts / Salivation / Side-Population Cells / Submandibular Gland (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1600-0714.2011.01011.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21884259 ● Search Scopus @ Elsevier (PMID): 21884259 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1600-0714.2011.01011.x (DOI: 10.1111/j.1600-0714.2011.01011.x, PubMed: 21884259)
19.	Mileva Ratko Karabasil, Takahiro Hasegawa, Ahmad Azlina, Nunuk Purwanti, Chenjuan Yao, Tetsuya Akamatsu, Shigemasa Tomioka and Kazuo Hosoi : Effects of naturally occurring G103D point mutation of AQP5 on its water permeability, trafficking, and cellular localization in the submandibular gland of rats, Biology of the Cell, Vol.103, No.2, 69-86, 2011. (Summary) AQPs (aquaporins) are water channel proteins that are expressed in almost all living things. In mammalians, 13 members of AQPs (AQP0-12) have been identified so far. AQP5 is known to be expressed mostly in the exocrine cells, including the salivary gland acinar cells. A naturally occurring point mutation (G308A, Gly103 > Asp103) was earlier found in the rat AQP5 gene [Murdiastuti, Purwanti, Karabasil, Li, Yao, Akamatsu, Kanamori and Hosoi (2006) Am. J. Physiol. 291, G1081-G1088]; in this mutant, the rate of initial saliva secretion under stimulated and unstimulated conditions is less than that for the wt (wild-type) animals. Here the mutant molecule was characterized in detail. Using the Xenopus oocyte system, we demonstrated the mutant AQP5 to have water permeability almost the same as that of the wt molecule. Mutant and wt AQP5s, tagged with GFP (green fluorescent protein; GFP-AQP5s) and expressed in polarized MDCK-II (Madin-Darby canine kidney II) cells, first appeared in the vesicular structure(s) in the cytoplasm, and were translocated to the upper plasma membrane or apical membrane during cultivation, with the mutant GFP-AQP5 being translocated less efficiently. Thapsigargin and H-89 both induced translocation in vitro of either molecule, whereas colchicine inhibited this activity; the fraction of cells showing apical localization of mutant GFP-AQP5 was less than that showing that of the wt molecule under any of the experimental conditions used. In the mutant SMG (submandibular gland) tissue, localization of AQP5 in the apical membrane of acinar cells was extremely reduced. Vesicular structures positive for AQP5 and present in the cytoplasm of the acinar cells were co-localized with LAMP2 (lysosome-associated membrane protein 2) or cathepsin D in the mutant gland, whereas such co-localizations were very rare in the wt gland, suggesting that the mutant molecules largely entered lysosomes for degradation. Replacement of highly conserved hydrophobic Gly103 with strongly hydrophilic Asp103 in rat AQP5, though it did not affect water permeability, may possibly have resulted in less efficient membrane trafficking and increased lysosomal degradation, leading to its lower expression in the apical membrane of the acinar cells in the SMG. (Keyword) Amino Acid Sequence / Animals / Aquaporin 5 / Cell Line / Cell Membrane / Dogs / Molecular Sequence Data / Mutation, Missense / Permeability / Point Mutation / Protein Transport / Rats / Sequence Alignment / Submandibular Gland / Water / Xenopus (Link to Publication Site) ● Publication site (DOI): 10.1042/BC20100086 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21138418 ● Search Scopus @ Elsevier (PMID): 21138418 ● Search Scopus @ Elsevier (DOI): 10.1042/BC20100086 (DOI: 10.1042/BC20100086, PubMed: 21138418)
20.	Ahmad Azlina, Purevjav Javkhlan, Yuka Hiroshima, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Roles of lysosomal proteolytic systems in AQP5 degradation in the submandibular gland of rats following chorda tympani parasympathetic denervation, American Journal of Physiology, Gastrointestinal and Liver Physiology, Vol.299, No.5, G1106-G1117, 2010. (Summary) Chorda tympani denervation (CTD) of rats was earlier shown to result in loss of submandibular gland (SMG) weight (at only 1 wk) and in continued reduction in aquaporin 5 (AQP5) protein expression (until 4 wk), without affecting its mRNA synthesis (Li X, Azlina A, Karabasil MR, Purwanti N, Hasegawa T, Yao C, Akamatsu T, Hosoi K. Am J Physiol Gastrointest Liver Physiol 295: G112-G123, 2008). The present study indicated that despite elevation of bax, a proapoptosis protein, by CTD, the operation also increased the level of bcl-2, an antiapoptosis protein, in the SMG. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) showed no increase in the number of apoptotic cells in the SMG. CTD, however, induced strongly and transiently (at 1-3 days) the protein expression of LC3B-II, a marker protein of autophagosomes, suggesting that the reduction in the gland weight was due to onset of autophagy by CTD. Upon CTD, Lamp2, a lysosomal marker, gradually increased in amount, reaching a peak at the 14th day. Immunohistochemical analysis revealed an increase in the number of lysosome-like structures positive for both AQP5 and Lamp2 in the acinar cells of the SMG after CTD; similar changes were observed also for AQP5 and LC3Bs. These data suggest that AQP5 in the SMG entered autophagosomes and/or lysosomes for degradation upon CTD. In vitro AQP5-degrading activity was found in the SMG extracts, and such activity was shown to be increased by CTD. Inhibitor experiments implied cathepsins B and L to be candidate enzymes for this degradation under normal and CTD conditions, respectively. (Keyword) Animals / Apoptosis / Aquaporin 5 / Blotting, Western / Chorda Tympani Nerve / Immunohistochemistry / In Situ Nick-End Labeling / Lysosomal-Associated Membrane Protein 2 / Lysosomes / Male / Parasympathectomy / Proto-Oncogene Proteins c-bcl-2 / Rats / Rats, Sprague-Dawley / Submandibular Gland (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpgi.00194.2010 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20689061 ● Search Scopus @ Elsevier (PMID): 20689061 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpgi.00194.2010 (DOI: 10.1152/ajpgi.00194.2010, PubMed: 20689061)
21.	Chenjuan Yao, Nunuk Purwanti, Mileva Ratko Karabasil, Ahmad Azlina, Javkhlan Purevjav, Takahiro Hasegawa, Tetsuya Akamatsu, Toru Hosoi, Koichiro Ozawa and Kazuo Hosoi : Potential down-regulation of salivary gland AQP5 by LPS via cross-coupling of NF-κB and p-c-Jun/c-Fos, The American Journal of Pathology, Vol.177, No.2, 724-734, 2010. (Summary) The mRNA and protein levels of aquaporin (AQP)5 in the parotid gland were found to be potentially decreased by lipopolysaccharide (LPS) in vivo in C3H/HeN mice, but only weakly in C3H/HeJ, a TLR4 mutant mouse strain. In the LPS-injected mice, pilocarpine-stimulated saliva production was reduced by more than 50%. In a tissue culture system, the LPS-induced decrease in the AQP5 mRNA level was blocked completely by pyrrolidine dithiocarbamate, MG132, tyrphostin AG126, SP600125, and partially by SB203580, which are inhibitors for IkappaB kinase, 26S proteasome, ERK1/2, JNK, and p38 MAPK, respectively. In contrast, the expression of AQP1 mRNA was down-regulated by LPS and such down-regulation was blocked only by SP600125. The transcription factors NF-kappaB (p65 subunit), p-c-Jun, and c-Fos were increased by LPS given in vivo, whereas the protein-binding activities of the parotid gland extract toward the sequences for NF-kappaB but not AP-1-responsive elements present at the promoter region of the AQP5 gene were increased by LPS injection. Co-immunoprecipitation by using antibody columns suggested the physical association of the three transcription factors. These results suggest that LPS-induced potential down-regulation of expression of AQP5 mRNA in the parotid gland is mediated via a complex(es) of these two classes of transcription factors, NF-kappaB and p-c-Jun/c-Fos. (Keyword) Animals / Aquaporin 1 / Aquaporin 5 / Cells, Cultured / Enzyme Inhibitors / Humans / JNK Mitogen-Activated Protein Kinases / Lipopolysaccharides / Male / Mice / Mice, Inbred C3H / Mice, Inbred C57BL / NF-kappa B / Nitrates / Nitrites / Proto-Oncogene Proteins c-fos / Salivary Glands (Link to Publication Site) ● Publication site (DOI): 10.2353/ajpath.2010.090282 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20522648 ● Search Scopus @ Elsevier (PMID): 20522648 ● Search Scopus @ Elsevier (DOI): 10.2353/ajpath.2010.090282 (DOI: 10.2353/ajpath.2010.090282, PubMed: 20522648)
22.	Mileva Ratko Karabasil, Takahiro Hasegawa, Ahmad Azlina, Nunuk Purwanti, Javkhlan Purevjav, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Trafficking of GFP-AQP5 chimeric proteins conferred with unphosphorylated amino acids at their PKA-target motif (¹⁵²SRRTS) in MDCK-II cells, The Journal of Medical Investigation : JMI, Vol.56, No.1, 2, 55-63, 2009. (Summary) Three constructs having mutated PKA-target motif at (152)SRRTS of AQP5, an exocrine type water channel, were prepared and fused to C-terminus of green fluorescence protein cDNA to examine the effects of blocking of phosphorylation at (152)SRRTS (a consensus PKA-target motif of AQP5) on translocation or trafficking of the chimeric proteins expressed in the Madin-Darby canine kidney-II (MDCK-II) cells. H-89 treatment increased translocation of wild-type GFP-AQP5 to the apical membrane. All 3 mutant molecules translocated 1.5 to 2 times more than the control wild-type GFP-AQP5. Colchicine but not cytochalasin B inhibited the translocation of wild-type GFP-AQP5. Present results suggest dephosphorylation of this consensus sequence increase GFP-AQP5 translocation, and that microtubules but not microfilaments are involved in this event. (Keyword) Amino Acid Motifs / Amino Acids / Animals / Aquaporin 5 / Cell Line / Cell Membrane / Chimera / Colchicine / Cyclic AMP-Dependent Protein Kinases / Cytochalasin B / Dogs / Green Fluorescent Proteins / Isoquinolines / Kidney / Phosphorylation / Protein Transport / Sulfonamides (Tokushima University Institutional Repository) ● Metadata: 111308 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.55 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19262015 ● Search Scopus @ Elsevier (PMID): 19262015 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.55 (Tokushima University Institutional Repository: 111308, DOI: 10.2152/jmi.56.55, PubMed: 19262015)
23.	Tetsuya Akamatsu, Ahmad Azlina, Nunuk Purwanti, Mileva Ratko Karabasil, Takahiro Hasegawa, Chenjuan Yao and Kazuo Hosoi : Inhibition and transcriptional silencing of a subtilisin-like proprotein convertase, PACE4/SPC4, reduces the branching morphogenesis of and AQP5 expression in rat embryonic submandibular gland, Developmental Biology, Vol.325, No.2, 434-443, 2009. (Summary) The submandibular gland (SMG) develops through the epithelial-mesenchymal interaction mediated by many growth/differentiation factors including activin and BMPs, which are synthesized as inactive precursors and activated by subtilisin-like proprotein convertases (SPC) following cleavage at their R-X-K/R-R site. Here, we found that Dec-RVKR-CMK, a potent inhibitor of SPC, inhibited the branching morphogenesis of the rat embryonic SMG, and caused low expression of a water channel AQP5, in an organ culture system. Dec-RVKR-CMK also decreased the expression of PACE4, a SPC member, but not furin, another SPC member, suggesting the involvement of PACE4 in the SMG development. Heparin, which is known to translocate PACE4 in the extracellular matrix into the medium, and an antibody specific for the catalytic domain of PACE4, both reduced the branching morphogenesis and AQP5 expression in the SMG. The inhibitory effects of Dec-RVKR-CMK were partially rescued by the addition of recombinant BMP2, whose precursor is one of the candidate substrates for PACE4 in vivo. Further, the suppression of PACE4 expression by siRNAs resulted in decreased expression of AQP5 and inhibition of the branching morphogenesis in the present organ culture system. These observations suggest that PACE4 regulates the SMG development via the activation of some growth/differentiation factors. (Keyword) Amino Acid Chloromethyl Ketones / Animals / Aquaporin 5 / Extracellular Matrix / Furin / Gene Silencing / Heparin / Morphogenesis / Organ Culture Techniques / Proprotein Convertases / Rats / Rats, Sprague-Dawley / Submandibular Gland (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ydbio.2008.10.015 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19013448 ● Search Scopus @ Elsevier (PMID): 19013448 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ydbio.2008.10.015 (DOI: 10.1016/j.ydbio.2008.10.015, PubMed: 19013448)
24.	Shingo Kurabuchi, Edward W Gresik, Chenjuan Yao and Kazuo Hosoi : Hypophysectomy and hormonal therapy modulate mK1-immunoreactive duct cells in the mice sublingual glands, Journal of Molecular Histology, Vol.39, No.5, 499-507, 2008. (Summary) The immunocytochemical localization of a true tissue kallikrein, mK1, in mouse sublingual glands (SLGs) was examined following hypophysectomy and hormonal replacement therapy. In the glands of intact mice (14 weeks of age), mK1 was detected in the striated ducts (SDs). Full-fledged granular cells were scattered in the SDs of male mice (but not in those of female mice), showing a cellular mosaic distribution of mK1 with some being positive and others being negative. mK1 was also detected in transitional-type granular cells, though the secretory granules were too small and scarce to be visible by a light microscopy. Hypophysectomy in male mice resulted in the atrophy and loss of secretory granules in many SD cells. Granulation recovered after the repeated injection of 5alpha-dihydrotestosterone (DHT), 3,5,3'-triiodo-L: thyronine (T3), and dexamethasone (Dex), given either alone or in combination to the hypophysectomized mice. The concomitant injection of DHT and T3, with or without Dex, resulted in the reappearance of the full-fledged granular cells, only some of which were mK1-positive. Electron microscopy revealed mK1 to be present exclusively in the secretory granules of these mK1-positive cells, and no ultrastructural differences were observed between mK1-positive and mK1-negative full-fledged granular cells. These results show that the differentiation of the granular cell phenotype in the mouse SLG duct system requires the concomitant action of androgen and thyroid hormone and retards mK1 synthesis. (Keyword) Animals / Dexamethasone / Dihydrotestosterone / Female / Glucocorticoids / Hormone Replacement Therapy / Hypophysectomy / Male / Mice / Mice, Inbred ICR / Secretory Vesicles / Sex Characteristics / Sublingual Gland / Tissue Kallikreins / Triiodothyronine (Link to Publication Site) ● Publication site (DOI): 10.1007/s10735-008-9189-7 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18716886 ● Search Scopus @ Elsevier (PMID): 18716886 ● Search Scopus @ Elsevier (DOI): 10.1007/s10735-008-9189-7 (DOI: 10.1007/s10735-008-9189-7, PubMed: 18716886)
25.	Xuefei Li, Ahmad Azlina, Mileva Ratko Karabasil, Nunuk Purwanti, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic agonist, American Journal of Physiology, Gastrointestinal and Liver Physiology, Vol.295, No.1, G112-G123, 2008. (Summary) By chorda tympani denervation (CTD, parasympathectomy), the aquaporin 5 (AQP5), but not AQP1, protein level in the rat submandibular gland (SMG) was significantly decreased, dropping to 37% of that of the contralateral gland at 4 wk. The protein levels of AQP5 and AQP1 were not significantly affected by denervation of the cervical sympathetic trunk (sympathectomy). Administration of cevimeline hydrochloride, an M3 muscarinic receptor agonist (10 mg/kg for 7 days po), but not pilocarpine (0.3 mg/kg for 7 days po), recovered the AQP5 protein level reduced by CTD and increased the AQP1 protein level above the control one. The mRNA level of AQP5 was scarcely affected by CTD and cevimeline hydrochloride administration. Administration of chloroquine (50 mg/kg for 7 days po), a denaturant of lysosomes, increased the AQP5 protein level reduced by CTD. An extract obtained from the submandibular lysosomal fraction degraded the AQP5 protein in the total membrane fraction in vitro. These results suggest the possible regulation of the AQP5 protein level in the SMG by the parasympathetic nerves/M3 muscarinic receptor agonist and imply the involvement of lysosomal enzymes, but not a transcriptional mechanism, in this regulation. (Keyword) Animals / Aquaporin 1 / Aquaporin 5 / Chorda Tympani Nerve / Gene Expression Regulation / Lysosomes / Male / Muscarinic Agonists / Parasympathectomy / Pilocarpine / Quinuclidines / RNA, Messenger / Rats / Rats, Sprague-Dawley / Submandibular Gland / Sympathectomy / Thiophenes / Time Factors (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpgi.00359.2007 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18450949 ● Search Scopus @ Elsevier (PMID): 18450949 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpgi.00359.2007 (DOI: 10.1152/ajpgi.00359.2007, PubMed: 18450949)
26.	Tetsuya Akamatsu, Nunuk Purwanti, Mileva Ratko Karabasil, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : Temporospatially regulated expression of subtilisin-like proprotein convertase PACE4 (SPC4) during development of the rat submandibular gland, Developmental Dynamics, Vol.236, No.1, 314-320, 2007. (Summary) The temporospatial expression of PACE4, a member of the mammalian subtilisin-like proprotein convertase family involved in the activation of growth/differentiation factors, was investigated by in situ hybridization during the development of the rat submandibular gland (SMG). At the initiation stage (day 15.5 of gestation; E15), PACE4 was intensely expressed in the submandibular epithelium, but weakly expressed in the mesenchymal cells. At E16 when the branching morphogenesis becomes obvious, the expression of PACE4 in the mesenchyme was further decreased, although its level in the submandibular epithelium had not changed remarkably from that at E15. During the next stage of embryonic development (E17-E20), PACE4 was expressed in the cells derived from the submandibular epithelium, which include the proacinar, terminal tubular, and presumptive ductal cells. In the perinatal SMG, PACE4 was still expressed intensely in the terminal portion of the SMG containing the proacinar and terminal tubular cells, whereas its expression in the ductal cells was obviously decreased at the second postnatal day (P2) and at P6. Acinar cells expressing no PACE4 appeared, and their numbers increased following their development (P9-P20). At P30 when the PACE4 expression in the acinar cells was completely suppressed, its expression in the ductal cells became intense again. This temporospatially regulated expression of PACE4 suggests its apparent association with the proliferation, differentiation, and establishment of functional acinar and ductal cells of the SMG. (Keyword) Animals / Female / Gene Expression Regulation, Developmental / Gene Expression Regulation, Enzymologic / In Situ Hybridization / Morphogenesis / Pregnancy / Proprotein Convertases / RNA, Messenger / Rats / Rats, Sprague-Dawley / Submandibular Gland (Link to Publication Site) ● Publication site (DOI): 10.1002/dvdy.21008 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17083113 ● Search Scopus @ Elsevier (PMID): 17083113 ● Search Scopus @ Elsevier (DOI): 10.1002/dvdy.21008 (DOI: 10.1002/dvdy.21008, PubMed: 17083113)
27.	Kwartarini Murdiastuti, Nunuk Purwanti, Mileva Ratko Karabasil, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : A naturally occurring point mutation in the rat aquaporin 5 gene, influencing its protein production by and secretion of water from salivary glands, American Journal of Physiology, Gastrointestinal and Liver Physiology, Vol.291, No.6, GI1081-GI1088, 2006. (Summary) A greater than twofold diversity in the expression level of aquaporin 5 (AQP5) has been observed in the membrane fraction of the submandibular gland (SMG) in Sprague-Dawley rats (Murdiastuti K, Miki O, Yao C, Parvin MN, Kosugi-Tanaka C, Akamatsu T, Kanamori N, and Hosoi K. Pflügers Arch 445: 405-412, 2002). In the present study, breeding between brother and sister rats was repeated within high AQP5 producers and low ones to obtain inbred offspring. High- and low-producer rats from 3rd to 18th generations were used for experiments. By Western blotting, levels of AQP5 proteins in the parotid and lacrimal glands, and lungs were all low in low producers, whereas they were all high in high producers, implying genetic variations of the gene for this water channel. Despite this implication, AQP5 mRNA levels were almost the same between the two groups by Northern blotting, suggesting the irrelevance of transcriptional regulation for this diversity. AQP5 cDNAs from the SMGs of the two groups were sequenced. The nucleotide sequence of AQP5 cDNA from low producers indicated the existence of a point mutation at nt 308 (G308A), leading to a replacement of (103)Gly with (103)Asp in the third transmembrane domain, but no alteration was detected in the Kozak area. The existence of such a mutation was confirmed by the assessment of genomic DNA also. This mutation may have resulted in an abnormal membrane insertion or ineffective trafficking of AQP5, since the rats having this mutation showed extremely low membrane expression of AQP5 in the SMG acinar cells and decreased water secretion from their salivary glands. (Keyword) Amino Acid Sequence / Animals / Aquaporin 5 / Base Sequence / Body Water / Molecular Sequence Data / Point Mutation / Rats / Salivary Glands / Sequence Homology, Amino Acid / Structure-Activity Relationship (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpgi.00449.2005 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16901987 ● Search Scopus @ Elsevier (PMID): 16901987 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpgi.00449.2005 (DOI: 10.1152/ajpgi.00449.2005, PubMed: 16901987)
28.	Chisato Kosugi, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Protein kinase A-regulated membrane trafficking of a green fluorescent protein-aquaporin 5 chimera in MDCK cells, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol.1763, No.4, 337-344, 2006. (Summary) The green fluorescent protein (GFP) of the jellyfish, Aeqorea victoria, was used as an autofluorescent tag to track the trafficking of aquaporin 5 (AQP5), an exocrine gland-type water channel. Two groups of chimeric proteins were constructed; one in which GFP was fused to the amino-terminus of AQP5 (GFP-AQP5) and the other, in which it was fused to the carboxyl terminus of it (AQP5-GFP). In each group, 2 chimeras were produced, a wild-type AQP5 with its normal sequence and a mutant AQP5 having a mutated amino acid at 259, i.e., GFP-AQP5-T259A and AQP5-GFP-T259A. They were used to transfect Madin-Darby canine kidney (MDCK) cells. The GFP-AQP5 chimera was localized in the intracellular vesicles, which trafficked to the plasma membrane in response to N(6), 2'-O-dibutyryladenosine 3', 5'-cyclic monophosphate (dbcAMP). Membrane trafficking was inhibited by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquimolinesulfonamide (H-89) but not by palmitoyl-dl-carnitine chloride (PCC). In contrast, the AQP5-GFP chimera expressed in MDCK cells was localized constitutively on the plasma membrane. The cellular localization of the latter chimera was not affected by stimulation with dbcAMP in the presence or absence of H-89 or PCC. Replacement of Thr-259 with Ala-259 did not affect the dbcAMP-induced translocation of the chimeric protein, suggesting that phosphorylation of Thr-259 was not necessary for AQP5 trafficking under the present experimental conditions. Thus, the GFP-AQP5 chimera will be a useful tool to study AQP5 trafficking in vitro, whereas the constitutive membrane localization of the AQP5-GFP chimera suggests the importance of the carboxyl terminus of the AQP5 protein for its sorting, whether it is translocated to intracellular vesicles or to the plasma membrane. (Keyword) Animals / Aquaporin 5 / Cell Line / Cell Membrane / Cyclic AMP-Dependent Protein Kinases / Dogs / Green Fluorescent Proteins / Protein Transport / Recombinant Fusion Proteins (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbamcr.2006.02.005 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16603260 ● Search Scopus @ Elsevier (PMID): 16603260 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbamcr.2006.02.005 (DOI: 10.1016/j.bbamcr.2006.02.005, PubMed: 16603260)
29.	Chenjuan Yao, Mileva Ratko Karabasil, Nunuk Purwanti, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Tissue kallikrein mK13 is a candidate processing enzyme for the precursor of interleukin-1b in the submandibular gland of mice, The Journal of Biological Chemistry, Vol.281, No.12, 7968-7976, 2006. (Summary) By using Western blot analysis, high levels of 17.5- and 20-kDa interleukin-1beta (IL-1beta) proteins were detected in the submandibular gland (SMG) of mice. Despite this fact, the amount of pro-IL-1beta protein, a precursor of IL-1beta, with a molecular size of 35 kDa in this tissue was below the detectable level, although strong expression of pro-IL-1beta mRNA was observed. A large amount of 17.5-kDa IL-1beta also appeared in the saliva of mice injected with lipopolysaccharide, suggesting that this IL-1beta is a secretory form produced by the SMG. The protein for IL-1beta-converting enzyme, a processing enzyme for pro-IL-1beta, was expressed only at a low level in the SMG as compared with its level in various epithelial tissues or lipopolysaccharide-stimulated macrophages. On the other hand, mK1, mK9, mK13, and mK22, members of the kallikrein family, were detected strongly in the SMG but not in other tissues. By incubation with mK13, but not with mK1, mK9, or mK22, the 35-kDa pro-IL-1beta was cleaved into two major products with molecular masses of 17.5 and 22 kDa, and production was inhibited by phenylmethylsulfonyl fluoride, a serine protease inhibitor, but not by IL-1beta-converting enzyme inhibitors. A peptide segment corresponding to amino acid residues 107-121 of mouse pro-IL-1beta (107WDDDDNLLVCDVPIR) was cleaved by incubation with mK13, generating two peptides, 107WDDDDNL and 114LVCDVPIR. Therefore, kallikrein mK13 would appear to hydrolyze pro-IL-1beta between its Leu113 and Leu114 residues. The results of immunohistochemistry and an autonomic therapy experiment showed that IL-1beta and kallikrein mK13 were co-localized in the secretory granules of granular convoluted tubular cells. Our present results thus suggest kallikrein mK13 is a plausible candidate for the processing enzyme for pro-IL-1beta in the SMG of mice. (Keyword) Animals / Blotting, Western / Caspases / Electrophoresis / Enzyme Inhibitors / Enzyme-Linked Immunosorbent Assay / Epithelium / Hydrolysis / Immunoblotting / Immunohistochemistry / Interleukin-1 / Isoenzymes / Kallikreins / Leucine / Lipopolysaccharides / Macrophages / Mice / Mice, Inbred C3H / Models, Genetic / Peptides / Phenylmethylsulfonyl Fluoride / Protease Inhibitors / Protein Binding / RNA, Messenger / Reverse Transcriptase Polymerase Chain Reaction / Saliva / Serine Endopeptidases / Submandibular Gland / Time Factors / Tissue Kallikreins (Link to Publication Site) ● Publication site (DOI): 10.1074/jbc.M507705200 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16423834 ● Search Scopus @ Elsevier (PMID): 16423834 ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M507705200 (DOI: 10.1074/jbc.M507705200, PubMed: 16423834)
30.	Keiko Tsumura, Xuefei Li, Kwartarini Murdiastuti, Most Nahid Parvin, Tetsuya Akamatsu, Chenjuan Yao, Norio Kanamori, Kiyotoshi Inenaga, Hiroshi Yamashita and Kazuo Hosoi : Downregulation of AQP2 expression in the kidney of polydipsic STR/N mice, American Journal of Physiology, Renal Physiology, Vol.290, No.2, F478-F485, 2006. (Summary) Aquaporin-2 (AQP2) is responsible for the concentration of urine in the kidney collecting tubule under the regulation of vasopressin. The mRNA level of this water channel in polydipsic STR/N mice was extremely reduced compared with that in normal ICR mice. In male mice, reduction of the AQP2 mRNA level was not evident at 3 wk of age, at which time water intake was not increased. At 10 wk of age, however, the AQP2 mRNA level was reduced to 10% of that in control mice, whereas water intake was increased by 36%. At 44 wk, the water intake became five times that of the control ICR mice, and the AQP2 mRNA level in these polydipsic mice was only approximately 5% of control. Similar changes were observed in the AQP2 protein level, suggesting that the mRNA level of AQP2 reflects the protein level of AQP2. These inverse changes in the AQP2 mRNA level and water intake were also evident in female mice. The data imply that polydipsia in STR/N mice may have affected AQP2 mRNA transcription in the kidney, resulting in reduced AQP2 expression, which would contribute to a reduction in overretention of water. (Keyword) Age Factors / Animals / Aquaporin 2 / Aquaporins / Body Weight / Diuresis / Down-Regulation / Drinking Behavior / Female / Kidney / Male / Mice / Mice, Inbred ICR / Mice, Inbred Strains / Osmolar Concentration / Polyuria / RNA, Messenger / Reverse Transcriptase Polymerase Chain Reaction / Thirst (Link to Publication Site) ● Publication site (DOI): 10.1152/ajprenal.00029.2005 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16144968 ● Summary page in Scopus @ Elsevier: 2-s2.0-33644865281 (DOI: 10.1152/ajprenal.00029.2005, PubMed: 16144968, Elsevier: Scopus)
31.	Chenjuan Yao, Xuefei Li, Murdiastuti Kwartarini, Chisato Kosugi, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Lipopolysaccharide-induced elevation and secretion of Interleukin-1b in the submandibular gland of male mice, Immunology, Vol.116, No.2, 213-222, 2005. (Summary) The intraperitoneal injection of lipopolysaccharide (LPS) (400 microg/kg body weight) induced the expression of mRNAs of inflammatory cytokines such as interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha in the submandibular gland (SMG) of C3H/HeN mice but not that of C3H/HeJ mice, a mutant strain for Toll-like receptor-4 (TLR-4(-) mutant). The mRNA levels of these cytokines in the SMG of the wild-type mice increased as early as 3 hr after injection, peaked at 3-6 hr, and had decreased again by 24 hr. In this study, we particularly focused on IL-1beta, and induction by this endotoxin was investigated in detail. Denervation of the superior cervical trunk and chorda tympani nerve did not diminish the LPS-induced elevation of IL-1beta mRNA in the SMG, indicating the irrelevance of the central nervous system in this induction. TLR-4 mRNA and protein were shown to be strongly expressed in the SMG, suggesting the direct action of LPS on this gland. IL-1beta proteins were localized in the secretory granules of granular convoluted tubular (GCT) cells, and their molecular weights in the gland were 17.5 and 20 kDa. IL-1beta of the same size appeared in the saliva 6 hr after LPS injection in C3H/HeN but not in C3H/HeJ mice. The present study thus suggests that IL-1beta, an inflammation cytokine, is induced and secreted into the saliva in response to endotoxin injected intraperitoneally. (Keyword) Animals / Blotting, Western / Cytokines / Gene Expression Regulation / Injections, Intraperitoneal / Interleukin-1 / Lipopolysaccharides / Male / Mice / Mice, Inbred C3H / RNA, Messenger / Reverse Transcriptase Polymerase Chain Reaction / Saliva / Submandibular Gland (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1365-2567.2005.02212.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16162270 ● Search Scopus @ Elsevier (PMID): 16162270 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1365-2567.2005.02212.x (DOI: 10.1111/j.1365-2567.2005.02212.x, PubMed: 16162270)
32.	Chenjuan Yao, Wei Wei, Xuefei Li and Kazuo Hosoi : Acute phase protein induction by experimental inflammation in the salivary gland, Journal of Oral Pathology & Medicine, Vol.34, No.6, 364-367, 2005. (Summary) The submandibular gland (SMG) is a major salivary gland, which plays an important role in maintenance the oral health. In this study, we intended to explore the role of the SMG's defense system of the animals in which experimental inflammation is induced. The levels of mRNAs for inflammation cytokines and acute phase proteins were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The mRNAs for acute phase proteins were found to be increased in the SMG and extraorbital and intraorbital lacrimal gland (ELG and ILG) of rats at 24 h after subcutaneous injection of turpentine oil. The induction of mRNA for these inflammatory proteins by turpentine oil was preceded by a transient increase in the level of mRNAs for IL-1beta, IL-6 and TNF-alpha at 6 h after subcutaneous injection of the oil. Such cytokine induction was similarly seen by lipopolysaccharide (LPS) injection, and involvement of Toll-like receptor 4 (TLR4) was strongly suggested from experiment using C3H/HeJ mice, a TLR4-deficient mutant strain. The up-regulation of acute phase proteins and inflammation cytokines in the SMG, ELG and ILG by experimental inflammation suggests the existence of a strict defense system via the innate immune system in the SMG and other exocrine gland. (Keyword) Acute-Phase Proteins / Animals / Cysteine Proteinase Inhibitors / Cytokines / Interleukin-1 / Interleukin-6 / Irritants / Kininogens / Lacrimal Apparatus / Lipopolysaccharides / Male / Membrane Glycoproteins / Mice / Mice, Inbred C3H / Mice, Inbred Strains / Mice, Mutant Strains / Rats / Rats, Wistar / Receptors, Cell Surface / Sialadenitis / Submandibular Gland Diseases / Time Factors / Toll-Like Receptor 4 / Toll-Like Receptors / Tumor Necrosis Factor-alpha / Turpentine / Up-Regulation (Link to Publication Site) ● Publication site (DOI): 10.1111/j.1600-0714.2005.00321.x (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15946185 ● Search Scopus @ Elsevier (PMID): 15946185 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1600-0714.2005.00321.x (DOI: 10.1111/j.1600-0714.2005.00321.x, PubMed: 15946185)
33.	Most Nahid Parvin, Shingo Kurabuchi, Kwartarini Murdiastuti, Chenjuan Yao, Chisato Kosugi, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Subcellular redistribution of AQP5 by vasoactive intestinal polypeptide (VIP) in the Brunner's gland of the rat duodenum, American Journal of Physiology, Gastrointestinal and Liver Physiology, Vol.288, No.6, G1283-G1291, 2005. (Summary) Aquaporin (AQP)5, an exocrine-type water channel, was detected in the rat duodenum by Western blot analysis, and was localized by immunohistochemistry in the secretory granule membranes as well as in the apical and lateral aspects of the plasma membrane of Brunner's gland cells. Incubation of duodenal slices with vasoactive intestinal polypeptide (VIP) in vitro significantly increased the amount of AQP5 in the apical membrane fraction in a dose- and time-dependent manner with the amount reaching a plateau at 100 nM VIP and becoming near maximal after a 30-s incubation. Protein kinase inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7, 50 muM), and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89; PKA-specific, 1 muM) blocked this increase, but PKC-specific inhibitor calphostin C did not, implying the involvement of PKA but not PKC in this cellular event. Intravenous injection with VIP (40 mug/kg body wt) provoked dilation of the lumen of the Brunner's gland at 2 and 7 min and increased the staining intensity of AQP5 in the apical and lateral membranes. AQP1 (both nonglycosylated and glycosylated forms) was also found to localize in the apical and basolateral membranes of cells of Brunner's gland. VIP, however, did not provoke any significant change in the AQP1 level in the apical membrane, as judged from the results of the above in vitro and in vivo experiments. These results suggest that VIP induced the exocytosis of granule contents and simultaneously caused translocation of AQP5 but not of AQP1 to the apical membrane in Brunner's gland cells. (Keyword) Animals / Aquaporin 1 / Aquaporin 5 / Aquaporins / Brunner Glands / Dose-Response Relationship, Drug / Exocytosis / Intracellular Signaling Peptides and Proteins / Male / Membrane Proteins / Protein Kinases / Rats / Rats, Sprague-Dawley / Vasoactive Intestinal Peptide (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpgi.00030.2004 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15650134 ● Search Scopus @ Elsevier (PMID): 15650134 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpgi.00030.2004 (DOI: 10.1152/ajpgi.00030.2004, PubMed: 15650134)
34.	Tetsuya Akamatsu, Most Nahid Parvin, Kwartarini Murdiastuti, Chisato Kosugi, Chenjuan Yao, Osamu Miki, Norio Kanamori and Kazuo Hosoi : Expression and localization of aquaporins, members of the water channel family, during development of the rat submandibular gland., Pflügers Archiv : European Journal of Physiology, Vol.446, No.6, 641-651, 2003. (Summary) The expression and localization of aquaporins (AQP1-AQP5), members of the water channel family, in the developing rat submandibular gland were analysed using RT-PCR, Northern blotting and immunohistochemistry to explore their relation to the development of this salivary gland. RT-PCR analysis revealed unique expression patterns of each AQP. AQP1 was expressed constitutively during prenatal development, whereas the expression of AQP5 became more intense in the course of development from embryonic day 16.5 (E16) to E20. These expression patterns concurred with the results of Northern blot analysis. AQP3 and AQP4 mRNAs in the prenatal development were not detected in Northern blots, although they were detected by RT-PCR. During postnatal development, AQP5 and AQP1 mRNAs were expressed continuously, but no message for AQP3 or AQP4 was detected. AQP2 mRNA was not detected during either prenatal or postnatal development in this tissue. Immunohistochemical studies revealed that AQP5 was first localized at the apical membrane of proacinar cells at E18, and then became clearly distributed at the apical membrane of acinar cells in accordance with the differentiation and establishment of the mature acini. In addition, some vasculature also showed immunoreactivity for AQP5. AQP1 was immunolocalized in the blood vessels, including capillaries, of the gland throughout development. These observations suggest the existence of transcriptional regulation of rat AQP5, which is one of the most probable regulators of saliva production and secretion, during the establishment of the functional submandibular salivary gland. (Keyword) Aging / Amino Acid Sequence / Animals / Aquaporins / Biological Transport, Active / Blotting, Northern / Body Water / Female / Immunohistochemistry / Molecular Sequence Data / Pregnancy / RNA / RNA, Antisense / Rats / Rats, Sprague-Dawley / Reverse Transcriptase Polymerase Chain Reaction / Sodium-Potassium-Exchanging ATPase / Submandibular Gland (Link to Publication Site) ● Publication site (DOI): 10.1007/s00424-003-1109-9 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12838423 ● Search Scopus @ Elsevier (PMID): 12838423 ● Search Scopus @ Elsevier (DOI): 10.1007/s00424-003-1109-9 (DOI: 10.1007/s00424-003-1109-9, PubMed: 12838423)
35.	Kwartarini Murdiastuti, Osamu Miki, Chenjuan Yao, Most Nahid Parvin, Chisato Kosugi, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Divergent expression and localization of aquaporin 5, an exocrine-type water channel, in the submandibular gland of Sprague-Dawley rats., Pflügers Archiv : European Journal of Physiology, Vol.445, No.3, 405-412, 2002. (Summary) 正常SDラット唾液腺(顎下腺)のAQP5蛋白質発現レベルを調べた所，高発現ラットおよび低発現ラットが存在する事を見いだした．2種のラットを近交化する目的で兄妹交配を進め，現在高発現ラットは8代目に，また低発現ラットは4代目に到った．これらのラットでは発現レベルの差は100倍以上に達した．AQP5蛋白質発現レベルの差は耳下腺，肺，涙腺においても認められたが，AQP5 mRNAレベルはいずれの臓器においても両グループ間で差はなかった．したがって，上記2グループ間で認められたAQP5蛋白質発現レベルの差異はAQP5遺伝子あるいはそのプロモーターに発生した遺伝的変異に基づくものと考えられた． (Keyword) aquaporin 5 / genetic variation / Sprague-Dawley (SD) rat / submandibular gland / KIDNEY COLLECTING DUCT / MOLECULAR-CLONING / FUNCTIONAL EXPRESSION / BASOLATERAL MEMBRANE / EPITHELIAL-CELLS / LACRIMAL GLANDS / PROTEIN / IMMUNOLOCALIZATION / GLYCEROL / UREA (Link to Publication Site) ● Publication site (DOI): 10.1007/s00424-002-0940-8 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1007/s00424-002-0940-8 (DOI: 10.1007/s00424-002-0940-8)

Academic Paper (Unrefereed Paper):

1.	Chenjuan Yao, Tetsuya Akamatsu, Takahiro Hasegawa and Hiroshi Yoshimura : The Defense System of Oral Cavity: Lipopolysaccharide Induced Inflammatory Response in the Mice Salivary Gland, BIT's 1st Annual World Congress of Oral & Dental Medicine Conference Abstract Book, 107, 2014. (Keyword) salivary gland / inflammation / inflammatory cytokine / Lipopolysaccharide
2.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Salivary Gland Development, Differentiation, and Regeneration - Role of Subtilisin-like Proprotein Convertase PACE4/SPC4, BIT's 1st Annual World Congress of Oral & Dental Medicine Conference Abstract Book, 59, 2014. (Keyword) salivary gland / development / differentiation / regeneration / Proprotein Convertase
3.	Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Hiroshi Yoshimura : Enhanced ubiquitylation and downregulation of aquaporin-5 by ubiquitin ligases, Journal of Oral Biosciences, Vol.Suppl., 204, 2014. (Keyword) water channel / ubiquitylation / downregulation / AQP5
4.	Chenjuan Yao, Tetsuya Akamatsu, Takahiro Hasegawa and Hiroshi Yoshimura : Expression of water channel AQP5 in regeneration model of salivary gland, Journal of Oral Biosciences, Vol.Suppl., 204, 2014. (Keyword) salivary gland / regeneration / water channel / AQP5
5.	Minegishi Makoto, Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Induced expression of subtilisin-like proprotein convertase in regeneration model of salivary gland, Journal of Oral Biosciences, Vol.Suppl., 138, 2014. (Keyword) salivary gland / regeneration / proprotein convertase

Review, Commentary:

1.	Kazuo Hosoi, Chenjuan Yao, Takahiro Hasegawa, Hiroshi Yoshimura and Tetsuya Akamatsu : Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions, International Journal of Molecular Sciences, Vol.21, No.4, 1182, Feb. 2020. (Tokushima University Institutional Repository) ● Metadata: 114575 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms21041182 (Link to Search Site for Scientific Articles) ● Summary page in Scopus @ Elsevier: 2-s2.0-85079334066 (Tokushima University Institutional Repository: 114575, DOI: 10.3390/ijms21041182, Elsevier: Scopus)
2.	Shingo Kurabuchi, Chenjuan Yao, Gang Chen and Kazuo Hosoi : Reversible Conversion among Subtypes of Salivary Gland Duct Cells as Identified by Production of a Variety of Bioactive Polypeptides, Acta Histochemica et Cytochemica, Vol.52, No.4, 59-65, Aug. 2019. (Summary) Four major kallikreins (mK1, mK22, mK9, and mK13) were identified in the mouse submandibular gland (SMG). mK1, a true tissue kallikrein, was used as a protein marker to identify different types of SMG granular convoluted tubule (GCT) cells along with epidermal growth factor (EGF), nerve growth factor (NGF), and renin. Kallikrein mK1 was localized in a very small number (~5%) of GCT cells, which were scattered throughout the GCT, indicating that the majority of GCT cells are mK1-negative. Among mK1-positive cells, particularly strong signals were observed in a small number of narrow cells, recognized as slender granular cells (SG cells, Type IV), in the GCT. After postnatal development of the SMG, GCT cells are no longer uniform based on the bioactive substances (mK1, EGF, NGF, and renin) that they produce and secrete. GCT cells were classified into four subtypes, Types I-IV, and it became clear that these subtypes are complicatedly and reversibly converted by the endocrine hormones 5α-dihydrotestosterone (DHT) and triiodothyronine (T). Duct segments with similar morphology or hormone dependency were recognized in the sublingual and parotid glands. The presence of duct cells with such characteristics is therefore a common feature of the three major salivary glands of rodents. (Keyword) 5α-dihydrotestosterone / epidermal growth factor / granular convoluted tubular cells / mK1 / submandibular gland (Tokushima University Institutional Repository) ● Metadata: 114977 (Link to Publication Site) ● Publication site (DOI): 10.1267/ahc.19014 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31602049 ● Search Scopus @ Elsevier (PMID): 31602049 ● Search Scopus @ Elsevier (DOI): 10.1267/ahc.19014 (Tokushima University Institutional Repository: 114977, DOI: 10.1267/ahc.19014, PubMed: 31602049)
3.	Kazuo Hosoi, Javkhlan Purevjav and Chenjuan Yao : Possible Existence of a Salivary Gland-Oral Mucosa/Gingiva Axis Under Challenges by Endotoxins, Journal of Molecular and Cellular Biology Forecast, Vol.1, No.1, 1002, Jan. 2018.
4.	Kazuo Hosoi and Chenjuan Yao : Suppression of aquaporin 5 gene expression by endotoxin via cross-coupling of transcription factors (In Japanese), Seikagaku, Vol.83, No.7, 632-638, Jul. 2011. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520009407217492352 ● Summary page in Scopus @ Elsevier: 2-s2.0-80053453855 (CiNii: 1520009407217492352, Elsevier: Scopus)
5.	Chenjuan Yao : Processing of IL-1beta by tissue kallikrein in the mouse submandibular gland, Shikoku Dental Research, Vol.19, No.2, 1-5, Jun. 2007. (Summary) We have shown earlier that the expression of interleukin-1β (IL-1β) mRNA is increased in the submandibular gland (SMG) after injection of lipopolysaccharide (LPS). In this present study we suggest that tissue kallikrein mK13 is a candidate of the processing enzyme for the precursor of IL-1β (pro-IL-1β) in the SMG. High levels of 17.5- and 20-kDa IL-1β proteins were detected by Western blotting in the SMG, and saliva from LPS-injected mice. Despite this fact, pro-IL-1β with a molecular size of 35-kDa was not detected in this tissue. The protein for IL-1β-converting enzyme (ICE) was expressed only at a low level in the SMG as compared with its level in various epithelial tissues or LPS-stimulated macrophages. We detected the strong expression of members of kallikrein family (mK1, mK9, mK13, and mK22) in the SMG but not other tissues. By incubation with mK13, but not with mK1, mK9, nor mK22, the 35-kDa pro-IL-1β was cleaved to give two major products with molecular masses of 17.5- and 22- kDa, which production was inhibited by PMSF, a serine protease inhibitor, but not by ICE inhibitors. The pro-IL-β peptide segment, which includes the putative processing site, was hydrolyzed at Leu^<113> and Leu^<114> by incubation with mK13. The immunohistochemistry and an autonomic therapy experiment showed that IL-1β and kallikrein mK13 were co-localized in the secretory granules of granular convoluted tubular cells. Our present results thus suggest that kallikrein mK13 is a plausible candidate for the processing enzyme for pro-IL-1β in the SMG of mice. (Keyword) IL-β / kallikrein / processing (Tokushima University Institutional Repository) ● Metadata: 287 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050001337462657664 (Tokushima University Institutional Repository: 287, CiNii: 1050001337462657664)

Proceeding of International Conference:

1.	Chenjuan Yao, Tetsuya Akamatsu, Takahiro Hasegawa and Hiroshi Yoshimura : Induced expression of a subtilisin-like proprotein convertase PACE4 in the regeneration model of rat submandibular gland., The 4th International Symposium on Salivary Glands in Honor of Niels Stensen, Okazaki (Japan), Nov. 2016.
2.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Sexual difference in the regeneration model of the rat submandibular gland., The 4th International Symposium on Salivary Glands in Honor of Niels Stensen, Okazaki (Japan), Nov. 2016.
3.	Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Hiroshi Yoshimura : Post-translational modifications of water channel aquaporin-5 in salivary gland cells, Oral Neuroscience 2016, Oral Neuroscience 2016, Osaka, Oct. 2016.
4.	Hiroshi Yoshimura, Tetsuya Akamatsu, Chenjuan Yao and Takahiro Hasegawa : Synaptic plasticity in the brain -Roles of NMDA receptor- (Invited lecture at Nantong University), Sep. 2016. (Keyword) synaptic plasticity / NMDA-receptors
5.	Chenjuan Yao, Tetsuya Akamatsu, Takahiro Hasegawa and Hiroshi Yoshimura : The Defense System of Oral Cavity: Lipopolysaccharide Induced Inflammatory Response in the Mice Salivary Gland, BIT's 1st Annual International Congress of Oral & Dental Medicine, Session 9: Oral Immunological Diseases, Allergy and Inflammation, Haikou, China, Nov. 2014. (Keyword) salivary gland / inflammation / inflammatory cytokine / Lipopolysaccharide
6.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Salivary Gland Development, Differentiation, and Regeneration - Role of Subtilisin-like Proprotein Convertase PACE4/SPC4, BIT's 1st Annual International Congress of Oral & Dental Medicine, Session 3: Oral Biology, Haikou, China, Nov. 2014. (Keyword) salivary gland / development / differentiation / regeneration / Proprotein Convertase
7.	Mileva Ratko Karabasil, Kwartarini Murdiastuti, Nunuk Purwanti, Azlina Ahmad, Javkhlan Purevjav, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Effects of natural point mutation of rat aquaporin 5 expressed in vitro on its capacity of water permeability and membrane trafficking, The Journal of Medical Investigation : JMI, Vol.56, No.Suppl, 398-400, Tokushima, Dec. 2009. (Summary) In the colony of Sprague-Dawley (SD) strain, we found that there were rats expressing a mutant AQP5, which has a point mutation at nt 308 (G308A), leading to a replacement of (103)Gly with (103)Asp in the 3rd transmembrane domain. The mutant molecule scarcely expressed in the acinar cells, probably because of ineffective trafficking. The mutant molecule, however, showed normal water permeability when assessed by the oocyte system. (Keyword) Amino Acid Sequence / Animals / Aquaporin 5 / Biological Transport / Cell Membrane Permeability / Female / Models, Animal / Molecular Sequence Data / Oocytes / Point Mutation / Rats / Rats, Sprague-Dawley / Submandibular Gland / water channel / Xenopus laevis (Tokushima University Institutional Repository) ● Metadata: 111488 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.398 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20224238 ● Search Scopus @ Elsevier (PMID): 20224238 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.398 (Tokushima University Institutional Repository: 111488, DOI: 10.2152/jmi.56.398, PubMed: 20224238)
8.	Purevjav Javkhlan, Yuka Hiroshima, Azlina Ahmad, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu, Jun-ichi Kido, Toshihiko Nagata and Kazuo Hosoi : Induction of calprotectin mRNAs by lipopolysaccharide in the salivary gland of mice, The Journal of Medical Investigation : JMI, Vol.56, No.Suppl, 287-289, Tokushima, Dec. 2009. (Summary) Calprotectin is a major cytosolic calcium-binding protein of leukocytes which belongs to the S100 protein family. S100A8 and S100A9, major types of calprotectin are heterodimeric complexes being composed of light- and heavy-chain subunits. The calprotectin levels in the plasma, feces, synovial fluid, gingival crevicular fluid, dental calculus and saliva change when the host animal suffers from several inflammatory diseases. Members of Toll-like receptor (TLR) family are pattern-recognition receptors for lipopolysaccharide (LPS) and other pathogens. Here we examined if the biological role of TLR receptor is reflected to the calprotectin expression in the salivary gland. Time course study by using real-time RT-PCR detected higher levels of S100A8 and S100A9 mRNA at 1.5-3 h after injection of LPS in both the submandibular gland (SMG) and parotid gland (PG) of C3H/HeN mice but not in the same tissues of C3H/HeJ, a TLR-4 mutant strain, indicating that this induction is mediated via the TLR-4. These results indicate that, an inflammatory marker, calprotectin, is expressed in the mouse salivary gland and that LPS stimulated its synthesis. Calprotectin (S100A8/A9) showed minimum expression in all cellular segments in the SMG except excretory duct cells, which showed strong signal at the cytoplasm. LPS induced their expressions in the granular convoluted tubular cells and striated duct cells. In the PG, these proteins were expressed very weakly in both duct and acinar cells with a little stronger staining for the former cells. LPS injection induced calprotectin (S100A8/A9) in both duct and acinar cells especially in the former cells. (Keyword) Animals / Calgranulin A / Calgranulin B / Leukocyte L1 Antigen Complex / Lipopolysaccharides / Mice / Mice, Inbred C3H / Mice, Mutant Strains / Parotid Gland / RNA, Messenger / salivary glands / Submandibular Gland / Toll-Like Receptor 4 (Tokushima University Institutional Repository) ● Metadata: 111354 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.287 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20224205 ● Search Scopus @ Elsevier (PMID): 20224205 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.287 (Tokushima University Institutional Repository: 111354, DOI: 10.2152/jmi.56.287, PubMed: 20224205)
9.	Azlina Ahmad, Xuefei Li, Purevjav Javkhlan, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Down-regulation of submandibular gland AQP5 following parasympathetic denervation in rats, The Journal of Medical Investigation : JMI, Vol.56, No.Suppl, 273-276, Tokushima, Dec. 2009. (Summary) Following chorda tympani denervation (CTD, parasympathetomy), the protein levels of aquaporin5 (AQP5) as well as AQP1 and Na(+)K(+)ATPase alpha-subunit in the rat submandibular gland (SMG) were found to be decreased significantly. However, the level of another membrane protein, dipeptidyl peptidase IV was not affected by CTD, suggesting a selective reduction of AQP5, AQP1, and Na(+)K(+)ATPase alpha -subunit proteins by CTD. However, the AQP5 mRNA level was scarcely affected by CTD, which suggested that transcription process of AQP5 was unaffected by this operation. AQP5 protein was shown to be degraded in vitro by the extract of the SMG obtained from normal rat; inhibitor experiments in vitro suggested cathepsin B was a responsible enzyme. Co-localization of AQP5 and LAMP-2, a lysosomal marker, implicated AQP5 is degraded in lysosomes. A significant increase in the protein levels of LC3-II, an autophagy marker, at day 1 after CTD, and co-localization of the LC3 protein and AQP5, suggested that CTD activated autophagy of SMG, leading to AQP5 degradation. (Keyword) Animals / Aquaporin 1 / Aquaporin 5 / autophagy / Chorda Tympani Nerve / Down-Regulation / Lysosomal-Associated Membrane Protein 2 / Male / Microtubule-Associated Proteins / Parasympathectomy / RNA, Messenger / Rats / Rats, Sprague-Dawley / Sodium-Potassium-Exchanging ATPase / Submandibular Gland (Tokushima University Institutional Repository) ● Metadata: 111348 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.273 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20224200 ● Search Scopus @ Elsevier (PMID): 20224200 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.273 (Tokushima University Institutional Repository: 111348, DOI: 10.2152/jmi.56.273, PubMed: 20224200)
10.	Nunuk Purwanti, Azlina Ahmad, Mileva Ratko Karabasil, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Involvement of the IL-6/STAT3/Sca-1 system in proliferation of duct cells following duct ligation in the submandibular gland of mice, The Journal of Medical Investigation : JMI, Vol.56, No.Suppl, 253-254, Tokushima, Dec. 2009. (Summary) Ligation of the main excretory duct (MED) of the mouse submandibular gland (SMG) induced the expression of Sca-1, a stem cell marker. Sca-1 expression increased prominently in almost all of cells in the duct system, except the acinar cells. Sca-1 induction was accompanied with phosphorylated-STAT3 (Y705) elevation, which was localized in the nuclei of all duct cells. Electrophoretic mobility shift assay (EMSA) confirmed the specific binding of STAT3 to the GAS sequence, a biding site of gamma interferon activating site. Present study suggested one of the initial steps of the tissue regeneration after injury includes STAT3 pathway. (Keyword) Animals / Antigens, Ly / Cell Proliferation / inflammation / Interleukin-6 / Ligation / male / Membrane Proteins / Mice / Mice, Inbred C57BL / regeneration / STAT3 Transcription Factor / signal transduction / Submandibular Gland (Tokushima University Institutional Repository) ● Metadata: 111340 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.253 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20224192 ● Search Scopus @ Elsevier (PMID): 20224192 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.253 (Tokushima University Institutional Repository: 111340, DOI: 10.2152/jmi.56.253, PubMed: 20224192)
11.	Tetsuya Akamatsu, Azlina Ahmad, Purevjav Javkhlan, Takahiro Hasegawa, Chenjuan Yao and Kazuo Hosoi : Salivary Gland Development: Its mediation by a subtilisin-like proprotein convertase, PACE4, The Journal of Medical Investigation : JMI, Vol.56, No.Suppl, 241-246, Tokushima, Dec. 2009. (Summary) The submandibular gland (SMG) develops under the epithelial-mesenchymal interaction. Its process is regulated by various growth/differentiation factors, which are synthesized as inactive precursors and activated via the limited proteolysis at their multi basic amino acid site(s) such as Arg-X-Lys/Arg-Arg. Although many of these processing steps are elucidated to be catalyzed by subtilisin-like proprotein convertases (SPCs), little is known about the role of SPCs in the SMG development. Here, we focused upon the physiological role of PACE4 (SPC4), a member of SPC family, in the SMG development. In the organ culture system of rat embryonic SMG (E15), Dec-RVKR-CMK, a potent inhibitor for SPCs, inhibited the salivary branching and the expression of an exocrine gland type water channel, AQP5. However, other peptidyl-CMKs and inhibitors for trypsin-like serine proteases including leupeptin did not affect the salivary branching and AQP5 expression. Dec-RVKR-CMK also suppressed the expression of PACE4, but not furin, another member of the family. The specific antibody for the catalytic domain of PACE4 suppressed the salivary branching and AQP5 expression similarly. These inhibitory effects of Dec-RVKR-CMK were partially rescued by the addition of recombinant BMP2 whose precursor is a candidate for the physiological substrates of PACE4. Further, the transcriptional silencing of PACE4 by its specific siRNAs caused the suppression of both the salivary branching and AQP5 expression in the present organ culture system. These observations strongly support the idea that PACE4 mediates the SMG development. (Keyword) Animals / Aquaporin 5 / Bone Morphogenetic Protein 2 / Morphogenesis / Proprotein Convertases / Rats / Salivary Glands / Signal Transduction (Tokushima University Institutional Repository) ● Metadata: 111337 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.241 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20224189 ● Search Scopus @ Elsevier (PMID): 20224189 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.241 (Tokushima University Institutional Repository: 111337, DOI: 10.2152/jmi.56.241, PubMed: 20224189)
12.	Chun Wang, Gang Chen, Junkang Jiang, Lianglin Qiu, Kazuo Hosoi and Chenjuan Yao : Aquaglyceroporins are involved in uptake of arsenite into murine gastrointestinal tissues, The Journal of Medical Investigation : JMI, Vol.56, No.Suppl, 343-346, Tokushima, Dec. 2009. (Summary) Aquaglyceroporins (AQGPs) are members of aquaporin (AQP) family and belong to a subgroup of this water channel family; they are transmembrane proteins that transport water as well as glycerol and other solutes of small molecules. Recent studies have also identified that AQGPs are important transporters of trivalent metalloid in some mammalian cells. However, the uptake routes of arsenite in mammals are still less defined. In this study, to understand the routes of arsenite intake in mammals, mice were treated with Hg(II), glycerol, and As(III) and uptake of As(III) into the gastrointestinal tissues was measured. The level of inorganic arsenic (iAs) in gastrointestinal tissues after As(III) stimulation was much higher than Hg(II) +As(III) or glycerol+As(III) group. RT-PCR results showed that AQGPs were extensively expressed in gastrointestinal tissues of mice. We also treated Caco-2 cells with Hg(II) and As(III); the level of iAs in a group treated with Hg(II)+As(III) decreased compared with As(III)-treated group. Our results suggested that AQGPs could be important transporters in arsenite uptake into gastrointestinal tissues of mice, but more data are need to prove if AQGPs is the only pathway involved in As transport in mammals or just one of them. (Keyword) Animals / Aquaglyceroporins / Arsenites / Biological Transport / Cell Line / Gastrointestinal Tract / Glycerol / Humans / Male / Mercury / Mice / Mice, Inbred ICR / Signal Transduction (Tokushima University Institutional Repository) ● Metadata: 111458 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.56.343 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20224220 ● Search Scopus @ Elsevier (PMID): 20224220 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.56.343 (Tokushima University Institutional Repository: 111458, DOI: 10.2152/jmi.56.343, PubMed: 20224220)
13.	Chenjuan Yao, Ahmad Azlina, Javkhlan Purevjav, Takahiro Hasegawa, Tetsuya Akamatsu and Kazuo Hosoi : Potential down-regulation of parotid gland AQP5 by LPS via cross-coupling of NF-κB/AP1, The 11th International Symposium on Exocrine Secretion, Tokushima 09 ''Exocrine Secretion Mechanism and Disease'', Tokushima, Jul. 2009.
14.	Ahmad Azlina, Nunuk Purwanti, Mileva R. Karabasil, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Is AQP5 down-regulated via autophagic pathway following chorda tympani denervation?, The International Symposium on Oral Sciences to Improve the Quality of Life, organized by Toshihiko Nagata, Tokushima, Sep. 2008.
15.	Mileva R. Karabasil, Takahiro Hasegawa, Ahmad Azlina, Nunuk Purwanti, Chenjuan Yao, Tetsuya Akamatsu, Shigemasa Tomioka and Kazuo Hosoi : Analyses of rat AQP5 G103D mutant expressed in MDCK-II cells and Xenopus oocytes, The International Symposium on Oral Sciences to Improve the Quality of Life, organized by Toshihiko Nagata, Tokushima, Sep. 2008.
16.	Nunuk Puwanti, Daisuke Tsuji, Mileva Ratko Karabasil, Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu, Kouji Itou and Kazuo Hosoi : Activation of IL-6/STAT3/Sca-1 system induces proliferation of duct cells in the duct-ligated mouse submandibular gland, The 2nd International Symposium on The Future Direction of Oral Sciences in The 21st Century-Oral Sciences for Our Healthy Life-, organized by Toshihiko Nagata, Tokushima, Dec. 2007.
17.	Mileva R. Karabasil, Kwartarini Murdiastuti, Takahiro Hasegawa, Nunuk Purwanti, Ahmad Azlina, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : A naturally occurring point mutation in rat AQP5 influencing its membrane trafficking in and water secretion from salivary gland, The 5th International Conference of Aquaporin, Nara, Jul. 2007.
18.	Xuefei Li, Ahmad Azlina, Mileva R. Karabasil, Nunuk Purwanti, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Effects of autonomic denervation and administration of M3 muscarinic receptor agonist on the AQP5 expression in the rat submandibular gland, The 5th International Conference of Aquaporin, Nara, Jul. 2007.
19.	Chenjuan Yao, Mileva R. Karabasil, Nunuk Purwanti, Ahmad Azlina, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : LPS induces down-regulation of AQP5 and AQP1 via Nf-kB and MAPK pathways in the mouse parotid gland, The 5th International Conference of Aquaporin, Nara, Jul. 2007.
20.	Tetsuya Akamatsu, Nunuk Purwanti, Ahmad Azlina, Mileva R. Karabasil, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : Prenatal expression of rat salivary AQP5 is dependent on the submandibular gland development mediated by a subtilisin-like proprotein convertase PACE4, The 5th International Conference of Aquaporin, Nara, Jul. 2007.
21.	Nunuk Puwanti, Daisuke Tsuji, Ahmad Azlina, Mileva Ratko Karabasil, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori, Kouji Itou and Kazuo Hosoi : Alterations of AQP5, cellular markers of duct, and Sca-1 expression in the duct-ligated mouse submandibular gland, The 5th International Conference of Aquaporin, Nara, Jul. 2007.
22.	Mileva R. Karabasil, Takahiro Hasegawa, Nunuk Purwanti, Kwartarini Murdiastuti, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Point mutation of AQP5 in Sprague-Dawley rats and its implication for salivary gland physiology, The 1st International Symposium and Workshop on The Future Direction of Oral Sciences in The 21st Century, organized by Bando, E., Awaji, Mar. 2007.
23.	Xuefei Li, Mileva R. Karabasil, Nunuk Purwanti, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Effects of autonomic denervation and administration of muscarinic receptor agonist on the expression of AQPs in the rat submandibular gland, The 1st International Symposium and Workshop on The Future Direction of Oral Sciences in The 21st Century, organized by Bando, E., Awaji, Mar. 2007.
24.	Nunuk Purwanti, Daisuke Tsuji, Mileva Ratko Karabasil, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori, Kouji Itou and Kazuo Hosoi : Changes of cellular markers of duct/acinni and side populations in the duct-ligated mouse submandibular gland, The 1st International Symposium and Workshop on The Future Direction of Oral Sciences in The 21st Century, organized by Bando, E., Awaji, Mar. 2007.
25.	Mileva R. Karabasil, Takahiro Hasegawa, Nunuk Purwanti, Kwartarini Murdiastuti, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Molecular and cellular analyses of mutant AQP5 which occurred naturally in Spraque - Dawley rats, 3rd International Symposium on Salivary Glands in Honor of Niels Stensen, Okazaki, Japan, Oct. 2006.
26.	Xuefei Li, Mileva R. Karabasil, Nunuk Purwanti, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Effects of autonomic denervation and administration of SNI-2011 on the expression of AQPs in the rat salivary gland, The 3rd International Symposium on Salivary Glands in honor of Niels Stensen, Okazaki, Japan, Oct. 2006.
27.	Chenjuan Yao, Mileva R. Karabasil, Nunuk Purwanti, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Tissue kallikrein mK13 is a candidate of the processing enzyme for pro-IL-1β in the mouse submandibular gland, The 3rd International Symposium on Salivary Glands in honor of Niels Stensen, Okazaki, Japan, Oct. 2006.
28.	Tetsuya Akamatsu, Nunuk Purwanti, Mileva R. Karabasil, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : Involvement of a subtilisin-like proprotein convertase, PACE4, in branching morphogenesis and AQP5 expression in the rat embryonic submandibular gland., The 3rd International Symposium on Salivary Glands in honor of Niels Stensen, Okazaki, Japan, Oct. 2006.
29.	Nunuk Purwanti, Daisuke Tsuji, Mileva Ratko Karabasil, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori, Kouji Itou and Kazuo Hosoi : The expression of cellular markers of duct/acini and side population dynamics in the duct-ligated mouse submandibular gland., 3rd International Symposium on Salivary Glands in Honor of Niels Stensen, Okazaki, Oct. 2006.
30.	Chenjuan Yao, Mileva R. Karabasil, Nunuk Purwanti, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Proteolytic processing of the precursor of interleukin-1β by tissue kallikrein mK13 in the submandibular gland of mice., International symposium on "Medical and Biological Perspectives in Proteases and Their Inhibitors", Satellite meeting of the 20th IUBMB International Congress of Biochemistry and Molecular Biology & the 11th FAOBMB Congress, Awaji, Japan, Jun. 2006.
31.	Tetsuya Akamatsu, Nunuk Purwanti, Mileva R. Karabasil, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : Inhibition of subtilisin-like proprotein convertase PACE4 reduces the branching morphogenesis and expression of AQP5 in the organ culture system of rat embryonic submandibular gland, International symposium on "Medical and Biological Perspectives in Proteases and Their Inhibitors", Satellite meeting of the 20th IUBMB International Congress of Biochemistry and Molecular Biology & the 11th FAOBMB Congress, Awaji, Japan, Jun. 2006.
32.	Tetsuya Akamatsu, Nunuk Purwanti, Mileva R. Karabasil, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : Inhibition of subtilisin-like proprotein convertase PACE4 reduces the branching morphogenesis and expression of AQP5 in the organ culture system of rat embryonic submandibular gland, 20th IUBMB International Congress of Biochemistry and Molecular Biology & 11th FAOBMB Congress, 第79回日本生化学会大会 & 第29回日本分子生物学会年会, also 第59回日本細胞生物学会大会, Kyoto, Jun. 2006.
33.	Chenjuan Yao, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Induction, processing, and secretion of IL-1βin the submandibular gland of mice, The 35th International Congress of Physiological Sciences (IUPS2005) and Experimental Biology 2005, San Diego, Mar. 2005.
34.	Tetsuya Akamatsu, Chenjuan Yao, Xuefei Li, Norio Kanamori and Kazuo Hosoi : ECM-bound proprotein convertase PACE4 is involved in the branching morphogenesis of rat submandibular gland, The 35th International Congress of Physiological Sciences (IUPS2005) and Experimental Biology 2005, San Diego, Mar. 2005.

Proceeding of Domestic Conference:

1.	平田愛佳, 佐藤匠, 増田尚輝, Chenjuan Yao, Rie Mukai, Takahito Watanabe, Taro Mito and Tetsuya Akamatsu : コオロギ食が唾液腺機能に及ぼす効果の検証, 第1回唾液ケア研究会学術集会, Nov. 2022.
2.	平田愛佳, 佐藤匠, 田中寛人, 増田尚輝, Chenjuan Yao, Rie Mukai, Takahiro Hasegawa, Hiroshi Yoshimura, Takahito Watanabe, Taro Mito and Tetsuya Akamatsu : 食品成分が唾液腺機能に及ぼす影響, 第34回唾液腺談話会, Sep. 2022.
3.	平田愛佳, 佐藤匠, 田中寛人, 小西冴季, Chenjuan Yao, Rie Mukai and Tetsuya Akamatsu : マウス唾液腺AQP5発現に及ぼす高脂肪食および低タンパク質食摂取の影響, 第63回歯科基礎医学会学術大会, Oct. 2021.
4.	Takako Fukuda, Shintaroh KUSUNOKI, 前田さおり, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Hiroshi Yoshimura : 周辺環境が主観的感覚および摂食行動に及ぼす影響:筋電図を用いた研究, 日本味と匂学会第55回大会, Sep. 2021.
5.	Kusunoki Shintaro, Fukuda Takako, Maeda Saori, Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu and Hiroshi Yoshimura : Relationship between brain activities and feeding behavior under comfortable and uncomfortable environments., 第55回日本味と匂い学会, Sep. 2021.
6.	平田愛佳, 佐藤匠, 田中寛人, 小西冴季, Chenjuan Yao, Rie Mukai and Tetsuya Akamatsu : 高脂肪食や低タンパク質食が引き起こすマウス唾液腺AQP5発現・局在変化, 第75回日本栄養・食糧学会大会, Jul. 2021.
7.	SATOH Takumi, Chenjuan Yao, Takahiro Hasegawa, Hiroshi Yoshimura and Tetsuya Akamatsu : Localization of subtilisin-like proprotein convertase PACE4 in the course of development of the rat submandibular gland, 第62回歯科基礎医学会学術大会, Sep. 2020.
8.	SATOH Takumi, Chenjuan Yao, Takahiro Hasegawa, Hiroshi Yoshimura and Tetsuya Akamatsu : Localization of subtilisin-like proprotein convertase PACE4 during development of the rat salivary gland, 第93回日本生化学会大会, Sep. 2020.
9.	Maeda Saori, Hiroshi Yoshimura, Miyaji Yuji, Hiroyuki Kanayama, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : Increase in theta-band EEG activities under tasting chocolate with unmatched odor stimulation, 第41回日本神経科学大会, Jul. 2018. (Keyword) electroencephalogram / theta wave
10.	前田さおり, Hiroshi Yoshimura, 宮地裕司, 金山宏幸, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : Theta band brain activity during checking the unmatched olfactory-taste information, 第95回日本生理学大会, Mar. 2018.
11.	前田さおり, 宮地裕司, 金山宏幸, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Hiroshi Yoshimura : 甘味とニオイのミスマッチが甘味認知に与える影響, 第69回日本生理学会中国・四国地方会, Oct. 2017.
12.	Mio Hata, Tetsuya Akamatsu, Chenjuan Yao, 前田さおり, 宮地裕司, 金山宏幸, Takahiro Hasegawa and Hiroshi Yoshimura : 唾液腺再生モデルにおける雌雄差の影響, 第69回日本生理学会中国・四国地方会, Oct. 2017.
13.	前田さおり, Hiroshi Yoshimura, 宮地ゆうじ, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : Influences of Match/Mismatch of taste and odor on taste perception: An electroencephalogram frequency analysis study, 日本味と匂学会第51回大会, Sep. 2017.
14.	Hiroshi Yoshimura, 須貝外喜夫, 加藤伸郎, 冨永貴志, 冨永洋子, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : カフェイン投与により誘発される視覚野オシレーションにおけるnon-NMDA受容体とNMDA受容体の相互交錯的関与, 第40回日本神経科学大会, Jul. 2017.
15.	Maeda Saori, Miyachi Yuki, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Hiroshi Yoshimura : Influences of olfactory stimulation on taste perception: An electroencephalogram frequency analysis study, The 94th Annual Meeting of the Physiological Science of Japan, Mar. 2017. (Keyword) taste perception / olfaction / electroencephalogram
16.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Sexual difference in regeneration of salivary gland, 第58回歯科基礎医学会学術大会, Aug. 2016.
17.	Tatsuya Shimatani, Makoto Minegishi, Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Induction of a subtilisin-like proprotein convertase PACE4 in regeneration model of salivary gland Part II, 第58回歯科基礎医学会学術大会, Aug. 2016.
18.	Hiroshi Yoshimura, 川邊真道, 須貝外喜夫, 加藤伸郎, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : Influences of oral impairment on neural oscilltion and wave propagation in the neocortex of rats, 第38回日本神経科学大会, Jul. 2015.
19.	Chenjuan Yao, Tetsuya Akamatsu, Takahiro Hasegawa and Hiroshi Yoshimura : Expression of water channel AQP5 in regeneration model of salivary gland, 第56回歯科基礎医学会, Sep. 2014. (Keyword) salivary gland / regeneration / water channel / AQP5
20.	Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Hiroshi Yoshimura : Enhanced ubiquitylation and downregulation of aquaporin-5 by ubiquitin ligases, 第56回歯科基礎医学会, Sep. 2014. (Keyword) water channel / ubiquitylation / downregulation / AQP5
21.	Minegishi Makoto, Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Induced expression of subtilisin-like proprotein convertase in regeneration model of salivary gland, 第56回歯科基礎医学会(福岡国際会議場/福岡県), Sep. 2014. (Keyword) salivary gland / regeneration / proprotein convertase
22.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Involvment of subtilisin-like proprotein convertase PACE4 in regeneration of salivary gland, 第55回歯科基礎医学会(2013年9月19日-21日), Sep. 2013.
23.	Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Hiroshi Yoshimura : ヒト唾液腺HSG細胞における構成的なAQP5の取り込み, 第55回歯科基礎医学会[2013年9月19日(金)-21日(日)], Sep. 2013.
24.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Involvment of subtilisin-like proprotein convertase PACE4 in regeneration of salivary gland, Journal of Oral Biosciences, Vol.55, No.Suppl., 199, Sep. 2013.
25.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Involvment of subtilisin-like proprotein convertase PACE4 in regeneration of salivary gland, 第55回歯科基礎医学会[2013年9月19日(金)-21日(日)], Sep. 2013.
26.	Hiroshi Yoshimura, 須貝外喜夫, Chenjuan Yao, Tetsuya Akamatsu, Takahiro Hasegawa and 加藤伸郎 : ラット大脳皮質におけるnon-NMDA受容体活動に依存する20Hzオシレーション, 第36回日本神経科学大会[2013年6月20日(木)-23日(日)], Jun. 2013.
27.	Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Hiroshi Yoshimura : ヒト唾液腺HSG細胞における構成的なAQP5の取り込み, Journal of Oral Biosciences, Vol.55, No.Suppl., 199, 2013.
28.	Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : 唾液腺細胞におけるアクアポリン5の翻訳後修飾, 第53回歯科基礎医学会学術大会サテライトシンポジウムSS11, Sep. 2011.
29.	Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : 唾液腺細胞におけるアクアポリン5の翻訳後修飾, Journal of Oral Biosciences, Vol.53, No.Supplement, 104, Sep. 2011.
30.	Purevjav Javkhlan, Yuka Hiroshima, Ahmad Azlina, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu, Toshihiko Nagata and Kazuo Hosoi : Calprotectin expression in the mouse salivary gland: Induction by lipopolysaccharide, 第52回歯科基礎医学会(2010年9月20-22日), Sep. 2010.
31.	Takahiro Hasegawa, Ahmad Azlina, Purevjav Javkhlan, Yuka Hiroshima, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : 唾液腺細胞におけるアクアポリン5リン酸化のシグナル伝達機構, 第52回歯科基礎医学会(2010年9月20-22日), Sep. 2010.
32.	Purevjav Javkhlan, Yuka Hiroshima, Ahmad Azlina, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu, Toshihiko Nagata and Kazuo Hosoi : Calprotectin expression in the mouse salivary gland: Induction by lipopolysaccharide, Journal of Oral Biosciences, Vol.52, No.supplement, 94, Sep. 2010.
33.	Takahiro Hasegawa, Ahmad Azlina, Javkhlan Purevjav, Yuka Hiroshima, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : 唾液腺細胞におけるアクアポリン5リン酸化のシグナル伝達機構, Journal of Oral Biosciences, Vol.52, No.supplement, 164, Sep. 2010.
34.	Chenjuan Yao, Ahmad Azlina, Javkhlan Purevjav, Takahiro Hasegawa, Tetsuya Akamatsu and Kazuo Hosoi : NF-κB/AP-1の複合体を介した耳下腺AQP5のLPSによるdown-regulation, 第51回歯科基礎医学会, Sep. 2009.
35.	Tetsuya Akamatsu, Ahmad Azlina, Javkhlan Purevjav, Takahiro Hasegawa, Chenjuan Yao and Kazuo Hosoi : 唾液腺の発生と細胞分化, 第51回歯科基礎医学会, Sep. 2009.
36.	Takahiro Hasegawa, Ahmad Azlina, Javkhlan Purevjav, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : アクアポリン5のユビキチン化とその細胞内膜輸送系における役割, 第51回歯科基礎医学会, Sep. 2009.
37.	Javkhlan Purevjav, Yuka Hiroshima, Ahmad Azlina, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu, Toshihiko Nagata and Kazuo Hosoi : Calprotectin induction by lipopolysaccharide in the salivary gland of mice, 第51回歯科基礎医学会, Sep. 2009.
38.	Ahmad Azlina, Javkhlan Purevjav, Takahiro Hasegawa, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : AQP5 degradation via autophagy following parasympathetic denervation in the rat SMG., 第51回歯科基礎医学会, Sep. 2009.
39.	カラバシルミレーバ, Takahiro Hasegawa, アズリナアハマド, プルワンティヌヌク, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : An AQP5 G103D mutant found in SD rats shows normal water permeability but reduced membrane trafficking, 第50回歯科基礎医学会, Sep. 2008.
40.	Chenjuan Yao, アズリナアハマド, プルワンティヌヌク, カラバシルミレーバ, Takahiro Hasegawa, Tetsuya Akamatsu and Kazuo Hosoi : 唾液腺AQP5のLPSによるdown-regulationの機構, 第50回歯科基礎医学会, Sep. 2008.
41.	アズリナアハマド, プルワンティヌヌク, カラバシルミレーバ, Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu and Kazuo Hosoi : Down regulation of submandibular gland AQP5 by chorda tympany denervation, 第50回歯科基礎医学会, Sep. 2008.
42.	プルワンティヌヌク, アズリナアハマド, カラバシルミレーバ, Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu and Kazuo Hosoi : Involvement of IL-6-STAT3-Sca-1 system in the proliferation of duct cells in the ligated mouse submandibular gland, 第50回歯科基礎医学会, Sep. 2008.
43.	Chenjuan Yao, アズリナアハマド, プルワンティヌヌク, カラバシルミレーバ, Takahiro Hasegawa, Tetsuya Akamatsu and Kazuo Hosoi : LPSによる耳下腺AQP5の発現制御とそのシグナル伝達経路, 第59回日本生理学会中国四国地方会, Nov. 2007.
44.	Tetsuya Akamatsu, アズリナアハマド, プルワンティヌヌク, カラバシルミレーバ, Takahiro Hasegawa, Chenjuan Yao and Kazuo Hosoi : 唾液腺腺房細胞の発生・分化・成熟化と水チャネルAQP5発現, 第59回日本生理学会中国四国地方会, Nov. 2007.
45.	プルワンティヌヌク, Daisuke Tsuji, アズリナアハマド, カラバシルミレーバ, Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu, Kouji Itou and Kazuo Hosoi : Transient increase in IL-6 by duct ligation leading to continuous elevation of Sca-1, a stem cells marker, in the mouse submandibular gland, 第49回歯科基礎医学会学術大会, Aug. 2007.
46.	カラバシルミレーバ, Takahiro Hasegawa, アズリナアハマド, プルワンティヌヌク, Chenjuan Yao, Tetsuya Akamatsu and Kazuo Hosoi : Analyses of function of rat mutant AQP5 expressed in MDCK II cells, 第49回歯科基礎医学会, Aug. 2007.
47.	アズリナアハマド, カラバシルミレーバ, プルワンティヌヌク, Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu and Kazuo Hosoi : Regulation of submandibular gland AQP5 protein expression by lysosomal system, 第49回歯科基礎医学会, Aug. 2007.
48.	Chenjuan Yao, アズリナアハマド, プルワンティヌヌク, カラバシルミレーバ, Takahiro Hasegawa, Tetsuya Akamatsu and Kazuo Hosoi : 唾液腺AQP5およびAQP1発現のLPSによるdown-regulation, 第49回歯科基礎医学会, Aug. 2007.
49.	Tetsuya Akamatsu, アズリナアハマド, プルワンティヌヌク, カラバシルミレーバ, Takahiro Hasegawa, Chenjuan Yao and Kazuo Hosoi : 唾液腺腺房細胞の分化とAQP5発現, 第49回歯科基礎医学会, Aug. 2007.
50.	カラバシルミレーバ, Takahiro Hasegawa, プルワンティヌヌク, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Functional analyses of rat mutant AQP5 expressed in vitro system and it's implication to abnormal saliva secretion, 第48回歯科基礎医学会, Sep. 2006.
51.	Xuefei Li, Nunuk Purwanti, Mileva R. Karabasil, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : ラット唾液腺AQP5，AQP1，及びリソゾーム酵素系に対する自律神経切除とSNI2011投与の影響, 第48回歯科基礎医学会, Sep. 2006.
52.	Chenjuan Yao, Mileva R. Karabasil, Nunuk Purwanti, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : LPSによる唾液腺AQP5およびAQP1の発現制御とそのシグナル伝達経路, 第48回歯科基礎医学会, Sep. 2006.
53.	Tetsuya Akamatsu, Nunuk Purwanti, Mileva R. Karabasil, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : 顎下腺の分枝形成とAQP5発現は前駆体蛋白質変換酵素PACE4により調節される, 第48回歯科基礎医学会, Sep. 2006.
54.	プルワンティヌヌク, Daisuke Tsuji, カラバシルミレーバ, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori, Kouji Itou and Kazuo Hosoi : Effect of duct ligation on the expression of cellular markers of duct/acini and side population dynamics of the mouse submandibular gland, 第48回歯科基礎医学会学術大会, Sep. 2006.
55.	Tetsuya Akamatsu, プルワンティヌヌク, カラバシルミレーバ, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : 唾液腺発生におけるsubtilisin-like proprotein convertaseの役割, 第28回分子生物学会年会, ワークショップW3G「プロテアーゼによる細胞分化・機能制御, 植物から動物まで/Proteases as biomodulators in bacteria, plant and animal」, Dec. 2005.
56.	Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Effects of sympathectomy, parasympathectomy, administration of SNI-2011 on the expression of AQP5 and AQP1 in the rat submandibular gland, 第78回日本生化学会大会, Oct. 2005.
57.	Chenjuan Yao, Nunuk Purwanti, Chisato Kosugi-Tanaka, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Kallikrein mK13 is a candidate of pro-IL-1βprocessing enzyme in the mouse salivary gland, 第78回日本生化学会大会, Oct. 2005.
58.	Tetsuya Akamatsu, Nunuk Purwanti, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : Developmental regulation of the submandibular gland by ECM-bound proprotein convertase PACE4, 第78回日本生化学会大会, Oct. 2005.
59.	Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : ラット顎下腺AQP5並びにAQP1に対する交感神経切除・副交感神経切除及びSNI-2011投与の影響, 第47回歯科基礎医学会, Sep. 2005.
60.	Chenjuan Yao, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : マウス唾液腺カリクレインmK13はpro-IL-1βプロセシング酵素の候補である, 第47回歯科基礎医学会, Sep. 2005.
61.	Tetsuya Akamatsu, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : 顎下腺発生における前駆体蛋白質変換酵素PACE4の関与, 第47回歯科基礎医学会, Sep. 2005.
62.	Kazuo Hosoi, Xuefei Li, Chenjuan Yao, Tetsuya Akamatsu, Norio Kanamori, ミレーバカラバシル and ヌヌクプルワンティ : 外分泌腺における水チャネル，アクアポリンの発現と機能調節, 第47回歯科基礎医学会サテライトシンポジウム「唾液分泌機構研究の最近の進歩」, Sep. 2005.
63.	Tetsuya Akamatsu, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : ECM-bound proprotein convertase PACE4 is a candidate regulator in the branching morphogenesis of rat submandibular gland, 第77回日本生化学会大会, Oct. 2004.
64.	Chenjuan Yao, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : マウス顎下腺におけるカリクレインmK13によるpro-IL1βの活性化, 第46回歯科基礎医学会, Sep. 2004.
65.	Tetsuya Akamatsu, Xuefei Li, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : 顎下腺の分枝形成と機能発現, 第46回歯科基礎医学会, Sep. 2004.
66.	Kawartarini Murdiastuti, Nahid Parvin, Chenjuan Yao, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : 水チャネル，アクアポリンの外分泌腺における発現と機能調節, 第45回日本生化学会中国・四国支部例会, May 2004.
67.	Tetsuya Akamatsu, Xuefei Li, Chenjuan Yao, Kawartarini Murdiastuti, Chisato Kosugi, Norio Kanamori and Kazuo Hosoi : ラット顎下腺の発生・分化・成熟と機能発現, 第45回日本生化学会中国・四国支部例会, May 2004.
68.	Chenjuan Yao, Xuefei Li, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : 実験的炎症による唾液腺サイトカインの誘導, 第45回歯科基礎医学会, Sep. 2003.
69.	Norio Kanamori, Tetsuya Akamatsu, Chisato Kosugi, Kawartarini Murdiastuti, Most. Nahid Parvin, Chenjuan Yao, Osamu Miki, Xuefei Li and Kazuo Hosoi : Jumping: An index behavior for the epileptic family of Mongolian gerbil. (Preliminary report), 第26回日本神経科学大会, Jul. 2003.
70.	Tetsuya Akamatsu, Most. Nahid Parvin, 小杉-田中知里, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : ラット顎下腺発生過程でのAQPsの発現と局在, 第75回日本生化学会大会, Oct. 2002.
71.	Kawartarini Murdiastuti, 三木修, Chenjuan Yao, Most. Nahid Parvin, 小杉-田中知里, Tetsuya Akamatsu, Norio Kanamori and Kazuo Hosoi : Divergent gene expression and localization of aquaporin 5 in the submandibular gland of Sprague-Dawley rats, 第44回歯科基礎医学会, Oct. 2002.
72.	Tetsuya Akamatsu, Most. Nahid Parvin, 小杉-田中知里, Chenjuan Yao, Norio Kanamori and Kazuo Hosoi : ラット顎下腺発生過程でのAQPsの発現と局在, 第44回歯科基礎医学会, Oct. 2002.
73.	Norio Kanamori, Tetsuya Akamatsu, 小杉-田中知里, Parvin Nahid Most., Chenjuan Yao and Kazuo Hosoi : 病態モデルスナネズミ近交化の試み(中間報告), 第25回日本神経科学大会, Jul. 2002.

Et cetera, Workshop:

1.	Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu and Hiroshi Yoshimura : マウス耳下腺における水チャネルAQP5のイソプロテレノールによるdouwn-regulationの機構, Journal of Oral Biosciences, Vol.54, No.Suppl., 153,
2.	Chenjuan Yao, 佐藤匠, Takahiro Hasegawa, Tetsuya Akamatsu and Hiroshi Yoshimura : イソプロパノール反復投与によるマウス唾液腺機能に及ぼす影響, 第34回唾液腺談話会, Sep. 2022. (Keyword) イソプロパノール / water channel
3.	Shimatani Tatsuya, Minegishi Makoto, Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Induction of a subtilisin-like proprotein convertase PACE4 in regeneration model of salivary gland Part II, Journal of Oral Biosciences, Vol.Suppl., 415, Aug. 2016.
4.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : Sexual difference in regeneration of salivary gland, Journal of Oral Biosciences, Vol.Suppl., 451, Aug. 2016.
5.	Tetsuya Akamatsu, Chenjuan Yao, Takahiro Hasegawa and Hiroshi Yoshimura : 唾液腺再生への subtilisin-like proprotein convertase PACE4の関与, 自然科学研究機構生理学研究所研究会「唾液腺形態形成研究会~機能解析から器官再生へ~」, Aug. 2014. (Keyword) salivary gland / regeneration / proprotein convertase
6.	Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu and Hiroshi Yoshimura : マウス耳下腺における水チャネルAQP5のイソプロテレノールによるdouwn-regulationの機構, 第54回歯科基礎医学会, Sep. 2012.
7.	Hiroshi Yoshimura, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : 細胞内cAMP上昇が大脳皮質味覚野から口腔体性感覚野への信号伝播速度に与える影響, 第54回歯科基礎医学会, Sep. 2012.
8.	Chenjuan Yao, Takahiro Hasegawa, Tetsuya Akamatsu and Hiroshi Yoshimura : マウス耳下腺における水チャネルAQP5のイソプロテレノールによるdouwn-regulationの機構, Journal of Oral Biosciences, Vol.54, No.Suppl., 153, Sep. 2012.
9.	Hiroshi Yoshimura, Takahiro Hasegawa, Chenjuan Yao and Tetsuya Akamatsu : 細胞内cAMP上昇が大脳皮質味覚野から口腔体性感覚野への信号伝播速度に与える影響, Journal of Oral Biosciences, Vol.54, No.Suppl., 131, Sep. 2012.

Report:

1.	Kazuo Hosoi, Norio Kanamori, Tetsuya Akamatsu and Chenjuan Yao : Molecular mechanism of expression and regulation of water channel, esp. aquaporins in the exocrine gland, , Report of research project, grant in-aid for scientific research (B), Tokushima, Mar. 2009.

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

フラボノイドの唾液腺機能亢進効果の検証:口腔乾燥症予防に資する機能性食品の開発 (Project/Area Number: 24K14725 )
Elucidation of Molecular Mechanism of the Salivary Gland Regeneration ~ Toward the application to the Regenerative Medicine for Xerostomia ~ (Project/Area Number: 26462814 )
Elucidation of the molecular mechanism on the differentiation/maturation and functional expression of salivary acinar cell toward conquest of xerostomia. (Project/Area Number: 23592737 )
Down-regulation of salivary glands AQP5 by LPS via NF-κB signaling (Project/Area Number: 20791353 )
Moecular meohanism of expression and regulation of the water channe1, aquapor in 5 in the exocrine gland (Project/Area Number: 18390493 )
Search by Researcher Number (20432750)

Assistant Professor : Yao, Chenjuan

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Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)