徳島大学 / 教育研究者総覧 --- 三宅雅人

専門分野

○	分子細胞生物学 (Molecular Cell Biology)

研究テーマ

○	小胞体ストレス応答による細胞機能調節

著書・論文

学術論文(審査論文):

1.	Mitsuaki Sobajima, Masato Miyake, Yoshimasa Hamada, Kazue Tsugawa, Miho Oyadomari, Ryota Inoue, Jun Shirakawa, Hiroshi Arima and Seiichi Oyadomari : The multifaceted role of ATF4 in regulating glucose-stimulated insulin secretion., Biochemical and Biophysical Research Communications, Vol.611, 165-171, 2022. (要約) Stress-inducible transcription factor ATF4 is essential for survival and identity of β-cell during stress conditions. However, the physiological role of ATF4 in β-cell function is not yet completely understood. To understand the role of ATF4 in glucose-stimulated insulin secretion (GSIS), β-cell-specific Atf4 knockout (βAtf4KO) mice were phenotypically characterized. Insulin secretion and mechanistic analyses were performed using islets from control Atf4f/f and βAtf4KO mice to assess key regulators for triggering and amplifying signals for GSIS. βAtf4KO mice displayed glucose intolerance due to reduced insulin secretion. Moreover, βAtf4KO islets exhibited a decrease in both the insulin content and first-phase insulin secretion. The analysis of βAtf4KO islets showed that ATF4 is required for insulin production and glucose-stimulated ATP and cAMP production. The results demonstrate that ATF4 contributes to the multifaceted regulatory process in GSIS even under stress-free conditions. (キーワード) Animals / Glucose / Glucose Intolerance / Insulin / Insulin Secretion / Insulin-Secreting Cells / Islets of Langerhans / Mice / Mice, Knockout (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bbrc.2022.04.038 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35489203 ● Search Scopus @ Elsevier (PMID): 35489203 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2022.04.038 (DOI: 10.1016/j.bbrc.2022.04.038, PubMed: 35489203)
2.	Masato Miyake, Mitsuaki Sobajima, Kiyoe Kurahashi, Akira Shigenaga, Masaya Denda, Akira Otaka, Tomohide Saio, Naoki Sakane, Hidetaka Kosako and Seiichi Oyadomari : Identification of an endoplasmic reticulum proteostasis modulator that enhances insulin production in pancreatic β cells., Cell Chemical Biology, Vol.29, No.6, 996-1009.e9, 2022. (要約) Perturbation of endoplasmic reticulum (ER) proteostasis is associated with impairment of cellular function in diverse diseases, especially the function of pancreatic β cells in type 2 diabetes. Restoration of ER proteostasis by small molecules shows therapeutic promise for type 2 diabetes. Here, using cell-based screening, we report identification of a chemical chaperone-like small molecule, KM04794, that alleviates ER stress. KM04794 prevented protein aggregation and cell death caused by ER stressors and a mutant insulin protein. We also found that this compound increased intracellular and secreted insulin levels in pancreatic β cells. Chemical biology and biochemical approaches revealed that the compound accumulated in the ER and interacted directly with the ER molecular chaperone BiP. Our data show that this corrector of ER proteostasis can enhance insulin storage and pancreatic β cell function. (キーワード) Diabetes Mellitus, Type 2 / Endoplasmic Reticulum / Endoplasmic Reticulum Stress / Humans / Insulin / Insulin-Secreting Cells / Proteostasis / Unfolded Protein Response (徳島大学機関リポジトリ) ● Metadata: 116761 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.chembiol.2022.01.002 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35143772 ● Search Scopus @ Elsevier (PMID): 35143772 ● Search Scopus @ Elsevier (DOI): 10.1016/j.chembiol.2022.01.002 (徳島大学機関リポジトリ: 116761, DOI: 10.1016/j.chembiol.2022.01.002, PubMed: 35143772)
3.	Masato Miyake, Jun Zhang, Akihiro Yasue, Satoshi Hisanaga, Kazue Tsugawa, Hiroshi Sakaue, Miho Oyadomari, Hiroshi Kiyonari and Seiichi Oyadomari : Integrated stress response regulates GDF15 secretion from adipocytes, preferentially suppresses appetite for a high-fat diet and improves obesity., iScience, Vol.24, No.12, 2021. (要約) The eIF2α phosphorylation-dependent integrated stress response (ISR) is a signaling pathway that maintains homeostasis in mammalian cells exposed to various stresses. Here, ISR activation in adipocytes improves obesity and diabetes by regulating appetite in a non-cell-autonomous manner. Adipocyte-specific ISR activation using transgenic mice decreases body weight and improves glucose tolerance and obesity induced by a high-fat diet (HFD) via preferential inhibition of HFD intake. The transcriptome analysis of ISR-activated adipose tissue reveals that growth differentiation factor 15 (GDF15) expression is induced by the ISR through the direct regulation of the transcription factors ATF4 and DDIT3. Deficiency in the GDF15 receptor GFRAL abolishes the adipocyte ISR-dependent preferential inhibition of HFD intake and the anti-obesity effects. Pharmacologically, 10(E), 12(Z)-octadecadienoic acid induces ISR-dependent GDF15 expression in adipocytes and decreases the intake of the HFD. Based on our findings the specific activation of the ISR in adipocytes controls the non-cell-autonomous regulation of appetite. (徳島大学機関リポジトリ) ● Metadata: 116908 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.isci.2021.103448 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34877504 ● Search Scopus @ Elsevier (PMID): 34877504 ● Search Scopus @ Elsevier (DOI): 10.1016/j.isci.2021.103448 (徳島大学機関リポジトリ: 116908, DOI: 10.1016/j.isci.2021.103448, PubMed: 34877504)
4.	Yu Saitou, Tetsuya Ikemoto, Kazunori Tokuda, Katsuki Miyazaki, Shin-ichiro Yamada, Satoru Imura, Masato Miyake, Yuji Morine, Seiichi Oyadomari and Mitsuo Shimada : Effective three-dimensional culture of hepatocyte-like cells generated from human adipose-derived mesenchymal stem cells., Journal of Hepato-Biliary-Pancreatic Sciences, Vol.28, No.9, 705-715, 2021. (要約) The aim of this study was to clarify the effectiveness of a new three-dimensional (3D) culture system for hepatocyte-like cells (HLCs) generated from human adipose-derived mesenchymal stem cells (ADSCs). Human ADSCs (2 × 10 ) with or without 0.1 mg/mL human recombinant peptide μ-piece per well were seeded in a 96-well U-bottom plate and then our three-step differentiation protocol was applied for 21 days. At each step, cell morphology and gene expression were investigated. Mature hepatocyte functions were evaluated after HLC differentiation. These parameters were compared between 2D- and 3D-cultured HLCs, and, DNA microarray analysis was also performed. Finally, HLCs were transplanted in to CCl induced acute liver failure model mice. Two-dimensional-cultured HLCs at day 21 did not have a spindle shape and had formed spheroids after day 6, which gradually increased in size for 3D-cultured HLCs. Definitive endoderm, hepatoblast, and hepatocyte genes showed significantly higher expression in the 3D culture group. Three-dimensional-cultured HLCs also had higher albumin expression, CYP3A4 activity, urea synthesis, and ammonium metabolism, and much higher expression of ion transporter, blood coagulation, and cell communication genes. HLC transplantation improved serum liver function, especially in T-Bil levels, and engrafted into immunodeficient mice with HLA class I positive staining. Our new 3D culture protocol is effective to improve hepatocyte functions. Our HLCs might be promising for clinical cell transplantation to treat metabolic disease. (出版サイトへのリンク) ● Publication site (DOI): 10.1002/jhbp.1024 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34318615 ● Search Scopus @ Elsevier (PMID): 34318615 ● Search Scopus @ Elsevier (DOI): 10.1002/jhbp.1024 (DOI: 10.1002/jhbp.1024, PubMed: 34318615)
5.	Thi Dinh Nguyen, Manh Thuong Le, Tsuyoshi Hattori, Mika Takarada-Iemata, Hiroshi Ishii, Jureepon Roboon, Takashi Tamatani, Takayuki Kannon, Kazuyoshi Hosomichi, Atsushi Tajima, Shusuke Taniuchi, Masato Miyake, Seiichi Oyadomari, Takashi Tanaka, Nobuo Kato, Shunsuke Saito, Kazutoshi Mori and Osamu Hori : The ATF6β-calreticulin axis promotes neuronal survival under endoplasmic reticulum stress and excitotoxicity., Scientific Reports, Vol.11, No.1, 2021. (要約) -binding capacity. CRT expression was reduced to ~ 50% in the CNS of Atf6b (徳島大学機関リポジトリ) ● Metadata: 116629 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-021-92529-w (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34158584 ● Search Scopus @ Elsevier (PMID): 34158584 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-021-92529-w (徳島大学機関リポジトリ: 116629, DOI: 10.1038/s41598-021-92529-w, PubMed: 34158584)
6.	Yoshimasa Hamada, Yuji Furumoto, Akira Izutani, Shusuke Taniuchi, Masato Miyake, Miho Oyadomari, Kenji Teranishi, Naoyuki Shimomura and Seiichi Oyadomari : Nanosecond pulsed electric fields induce the integrated stress response via reactive oxygen species-mediated heme-regulated inhibitor (HRI) activation., PLoS ONE, Vol.15, No.3, e0229948, 2020. (要約) The integrated stress response (ISR) is one of the most important cytoprotective mechanisms and is integrated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Four eIF2α kinases, heme-regulated inhibitor (HRI), double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and general control nonderepressible 2 (GCN2), are activated in response to several stress conditions. We previously reported that nanosecond pulsed electric fields (nsPEFs) are a potential therapeutic tool for ISR activation. In this study, we examined which eIF2α kinase is activated by nsPEF treatment. To assess the responsible eIF2α kinase, we used previously established eIF2α kinase quadruple knockout (4KO) and single eIF2α kinase-rescued 4KO mouse embryonic fibroblast (MEF) cells. nsPEFs 70 ns in duration with 30 kV/cm electric fields caused eIF2α phosphorylation in wild-type (WT) MEF cells. On the other hand, nsPEF-induced eIF2α phosphorylation was completely abolished in 4KO MEF cells and was recovered by HRI overexpression. CM-H2DCFDA staining showed that nsPEFs generated reactive oxygen species (ROS), which activated HRI. nsPEF-induced eIF2α phosphorylation was blocked by treatment with the ROS scavenger N-acetyl-L-cysteine (NAC). Our results indicate that the eIF2α kinase HRI is responsible for nsPEF-induced ISR activation and is activated by nsPEF-generated ROS. (徳島大学機関リポジトリ) ● Metadata: 114915 (出版サイトへのリンク) ● Publication site (DOI): 10.1371/journal.pone.0229948 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32155190 ● Search Scopus @ Elsevier (PMID): 32155190 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0229948 (徳島大学機関リポジトリ: 114915, DOI: 10.1371/journal.pone.0229948, PubMed: 32155190)
7.	Hironori Kato, Kohki Okabe, Masato Miyake, Kazuki Hattori, Tomohiro Fukaya, Kousuke Tanimoto, Shi Beini, Mariko Mizuguchi, Satoru Torii, Satoko Arakawa, Masaya Ono, Yusuke Saito, Takashi Sugiyama, Takashi Funatsu, Katsuaki Sato, Shigeomi Shimizu, Seiichi Oyadomari, Hidenori Ichijo, Hisae Kadowaki and Hideki Nishitoh : ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue., Life Science Alliance, Vol.3, No.3, e201900576, 2020. (要約) Mitochondria play a central role in the function of brown adipocytes (BAs). Although mitochondrial biogenesis, which is indispensable for thermogenesis, is regulated by coordination between nuclear DNA transcription and mitochondrial DNA transcription, the molecular mechanisms of mitochondrial development during BA differentiation are largely unknown. Here, we show the importance of the ER-resident sensor PKR-like ER kinase (PERK) in the mitochondrial thermogenesis of brown adipose tissue. During BA differentiation, PERK is physiologically phosphorylated independently of the ER stress. This PERK phosphorylation induces transcriptional activation by GA-binding protein transcription factor α subunit (GABPα), which is required for mitochondrial inner membrane protein biogenesis, and this novel role of PERK is involved in maintaining the body temperatures of mice during cold exposure. Our findings demonstrate that mitochondrial development regulated by the PERK-GABPα axis is indispensable for thermogenesis in brown adipose tissue. (徳島大学機関リポジトリ) ● Metadata: 115577 (出版サイトへのリンク) ● Publication site (DOI): 10.26508/lsa.201900576 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32029570 ● Search Scopus @ Elsevier (PMID): 32029570 ● Search Scopus @ Elsevier (DOI): 10.26508/lsa.201900576 (徳島大学機関リポジトリ: 115577, DOI: 10.26508/lsa.201900576, PubMed: 32029570)
8.	Keisuke Kitakaze, Shusuke Taniuchi, Eri Kawano, Yoshimasa Hamada, Masato Miyake, Miho Oyadomari, Hirotatsu Kojima, Hidetaka Kosako, Tomoko Kuribara, Suguru Yoshida, Takamitsu Hosoya and Seiichi Oyadomari : Cell-based HTS identifies a chemical chaperone for preventing ER protein aggregation and proteotoxicity., eLife, Vol.8, e43302, 2019. (要約) ]benzothiazole derivatives (IBTs) as chemical chaperones in a cell-based high-throughput screen. Biochemical and chemical biology approaches revealed that IBT21 directly binds to unfolded or misfolded proteins and inhibits protein aggregation. Finally, IBT21 prevented cell death caused by chemically induced ER stress and by a proteotoxin, an aggression-prone prion protein. Taken together, our data show the promise of IBTs as potent chemical chaperones that can ameliorate diseases resulting from protein aggregation under ER stress. (徳島大学機関リポジトリ) ● Metadata: 115090 (出版サイトへのリンク) ● Publication site (DOI): 10.7554/eLife.43302 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31843052 ● Search Scopus @ Elsevier (PMID): 31843052 ● Search Scopus @ Elsevier (DOI): 10.7554/eLife.43302 (徳島大学機関リポジトリ: 115090, DOI: 10.7554/eLife.43302, PubMed: 31843052)
9.	Satoshi Hisanaga, Masato Miyake, Shusuke Taniuchi, Miho Oyadomari, Masatoshi Morimoto, Ryosuke Sato, Jun Hirose, Hiroshi Mizuta and Seiichi Oyadomari : PERK-mediated translational control is required for collagen secretion in chondrocytes., Scientific Reports, Vol.8, No.1, 773, 2018. (要約) mice displayed reduced collagen in articular cartilage but no differences in chondrocyte proliferation or apoptosis compared to the findings in wild-type mice. PERK inhibition increases misfolded protein levels in the ER, which largely hinder ER-to-Golgi transport. These results suggest that the translational control mediated by PERK is a critical determinant of ECM secretion in chondrocytes. (徳島大学機関リポジトリ) ● Metadata: 112406 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-017-19052-9 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29335505 ● Summary page in Scopus @ Elsevier: 2-s2.0-85057222869 (徳島大学機関リポジトリ: 112406, DOI: 10.1038/s41598-017-19052-9, PubMed: 29335505, Elsevier: Scopus)
10.	Carina Fischer, Takahiro Seki, Sharon Lim, Masaki Nakamura, Patrik Andersson, Yunlong Yang, Jennifer Honek, Yangang Wang, Yanyan Gao, Fang Chen, J Nilesh Samani, Jun Zhang, Masato Miyake, Seiichi Oyadomari, Akihiro Yasue, Xuri Li, Yun Zhang, Yizhi Liu and Yihai Cao : A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning., Nature Communications, Vol.8, No.1, 2079, 2017. (要約) Understanding the molecular mechanisms regulating beige adipocyte formation may lead to the development of new therapies to combat obesity. Here, we report a miRNA-based autocrine regulatory pathway that controls differentiation of preadipocytes into beige adipocytes. We identify miR-327 as one of the most downregulated miRNAs targeting growth factors in the stromal-vascular fraction (SVF) under conditions that promote white adipose tissue (WAT) browning in mice. Gain- and loss-of-function experiments reveal that miR-327 targets FGF10 to prevent beige adipocyte differentiation. Pharmacological and physiological -adrenergic stimulation upregulates FGF10 levels and promotes preadipocyte differentiation into beige adipocytes. In vivo local delivery of miR-327 to WATs significantly compromises the beige phenotype and thermogenesis. Contrarily, systemic inhibition of miR-327 in mice induces browning and increases whole-body metabolic rate under thermoneutral conditions. Our data provide mechanistic insight into an autocrine regulatory signaling loop that regulates beige adipocyte formation and suggests that the miR-327-FGF10-FGFR2 signaling axis may be a therapeutic targets for treatment of obesity and metabolic diseases. (徳島大学機関リポジトリ) ● Metadata: 112463 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41467-017-02158-z (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29233981 ● Search Scopus @ Elsevier (PMID): 29233981 ● Search Scopus @ Elsevier (DOI): 10.1038/s41467-017-02158-z (徳島大学機関リポジトリ: 112463, DOI: 10.1038/s41467-017-02158-z, PubMed: 29233981)
11.	Masato Miyake, Masashi Kuroda, Hiroshi Kiyonari, Kenji Takehana, Satoshi Hisanaga, Masatoshi Morimoto, Jun Zhang, Miho Oyadomari, Hiroshi Sakaue and Seiichi Oyadomari : Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice., PLoS ONE, Vol.12, No.6, e0179955, 2017. (要約) As a novel model of muscle wasting, HSA-Fv2E-PERK Tg mice provide a convenient tool for studying the pathogenesis of muscle loss and for assessing putative therapeutics. (徳島大学機関リポジトリ) ● Metadata: 114340 (出版サイトへのリンク) ● Publication site (DOI): 10.1371/journal.pone.0179955 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28644884 ● Search Scopus @ Elsevier (PMID): 28644884 ● Search Scopus @ Elsevier (DOI): 10.1371/journal.pone.0179955 (徳島大学機関リポジトリ: 114340, DOI: 10.1371/journal.pone.0179955, PubMed: 28644884)
12.	Kiyoe Kurahashi, Seika Inoue, Sumiko Yoshida, Yasumasa Ikeda, Kana Morimoto, Ryoko Uemoto, Kazue Ishikawa, Takeshi Kondo, Tomoyuki Yuasa, Itsuro Endo, Masato Miyake, Seiichi Oyadomari, Toshio Matsumoto, Masahiro Abe, Hiroshi Sakaue and Ken-ichi Aihara : The Role of Heparin Cofactor in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice., Journal of Atherosclerosis and Thrombosis, 2017. (要約) The present studies provide evidence to support the idea that HC plays an important role in the maintenance of glucose homeostasis by regulating insulin sensitivity in both humans and mice. Stimulators of HC production may serve as novel therapeutic tools for the treatment of type 2 diabetes. (徳島大学機関リポジトリ) ● Metadata: 110925 (出版サイトへのリンク) ● Publication site (DOI): 10.5551/jat.37739 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28502917 ● Search Scopus @ Elsevier (PMID): 28502917 ● Search Scopus @ Elsevier (DOI): 10.5551/jat.37739 (徳島大学機関リポジトリ: 110925, DOI: 10.5551/jat.37739, PubMed: 28502917)
13.	Shusuke Taniuchi, Masato Miyake, Kazue Tsugawa, Miho Oyadomari and Seiichi Oyadomari : Integrated stress response of vertebrates is regulated by four eIF2α kinases., Scientific Reports, Vol.6, 32886, 2016. (要約) The integrated stress response (ISR) is a cytoprotective pathway initiated upon phosphorylation of the eukaryotic translation initiation factor 2 (eIF2α) residue designated serine-51, which is critical for translational control in response to various stress conditions. Four eIF2α kinases, namely heme-regulated inhibitor (HRI), protein kinase R (PKR), PKR-like endoplasmic reticulum kinase, (PERK) and general control non-depressible 2 (GCN2), have been identified thus far, and they are known to be activated by heme depletion, viral infection, endoplasmic reticulum stress, and amino acid starvation, respectively. Because eIF2α is phosphorylated under various stress conditions, the existence of an additional eIF2α kinase has been suggested. To validate the existence of the unidentified eIF2α kinase, we constructed an eIF2α kinase quadruple knockout cells (4KO cells) in which the four known eIF2α kinase genes were deleted using the CRISPR/Cas9-mediated genome editing. Phosphorylation of eIF2α was completely abolished in the 4KO cells by various stress stimulations. Our data suggests that the four known eIF2α kinases are sufficient for ISR and that there are no additional eIF2α kinases in vertebrates. (徳島大学機関リポジトリ) ● Metadata: 112371 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/srep32886 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27633668 ● Search Scopus @ Elsevier (PMID): 27633668 ● Search Scopus @ Elsevier (DOI): 10.1038/srep32886 (徳島大学機関リポジトリ: 112371, DOI: 10.1038/srep32886, PubMed: 27633668)
14.	Masato Miyake, Akitoshi Nomura, Atsushi Ogura, Kenji Takehana, Yoshihiro Kitahara, Kazuna Takahara, Kazue Tsugawa, Chinobu Miyamoto, Naoko Miura, Ryosuke Sato, Kiyoe Kurahashi, P Heather Harding, Miho Oyadomari, David Ron and Seiichi Oyadomari : Skeletal muscle-specific eukaryotic translation initiation factor 2 phosphorylation controls amino acid metabolism and fibroblast growth factor 21-mediated non-cell-autonomous energy metabolism., The FASEB journal, Vol.30, No.2, 798-812, 2015. (要約) The eukaryotic translation initiation factor 2 (eIF2) phosphorylation-dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand-activated skeletal muscle-specific derivative of the eIF2 protein kinase R-like ER kinase revealed the expected up-regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small-molecule ISR activator that promoted Fgf21 expression in cell-based screens and by implication of the ISR-inducible activating transcription factor 4 in the process. Our findings establish that eIF2 phosphorylation regulates not only cell-autonomous proteostasis and amino acid metabolism, but also affects non-cell-autonomous metabolic regulation by induced expression of a potent myokine.-Miyake, M., Nomura, A., Ogura, A., Takehana, K., Kitahara, Y., Takahara, K., Tsugawa, K., Miyamoto, C., Miura, N., Sato, R., Kurahashi, K., Harding, H. P., Oyadomari, M., Ron, D., Oyadomari, S. Skeletal muscle-specific eukaryotic translation initiation factor 2 phosphorylation controls amino acid metabolism and fibroblast growth factor 21-mediated non-cell-autonomous energy metabolism. (徳島大学機関リポジトリ) ● Metadata: 115105 (出版サイトへのリンク) ● Publication site (DOI): 10.1096/fj.15-275990 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26487695 ● Summary page in Scopus @ Elsevier: 2-s2.0-84958811791 (徳島大学機関リポジトリ: 115105, DOI: 10.1096/fj.15-275990, PubMed: 26487695, Elsevier: Scopus)
15.	H Takahashi, K Sato, T Yamaguchi, Masato Miyake, H Watanabe, Y Nagasawa, E Kitagawa, S Terada, M Urakawa, M T. Rose, C D. McMahon, K Watanabe, S Ohwada, T Gotoh and H Aso : Myostatin alters glucose transporter-4 (GLUT4) expression in bovine skeletal muscles and myoblasts isolated from double-muscled (DM) and normal-muscled (NM) Japanese shorthorn cattle., Domestic Animal Endocrinology, Vol.48, 62-68, 2014. (要約) The purpose of this study was to determine whether myostatin alters glucose transporter-4 (GLUT4) expression in bovine skeletal muscles and myoblasts isolated from double-muscled (DM) and normal-muscled (NM) Japanese Shorthorn cattle. Plasma concentrations of glucose were lower in DM cattle than in NM cattle (P < 0.01). The expression of GLUT4 messenger RNA (mRNA) in the skeletal muscle ex vivo and in myoblasts at 72 h after differentiation in vitro was higher in DM cattle than in NM cattle (P < 0.01). In contrast, the NM and DM cattle did not differ with respect to skeletal muscle expression of GLUT1 and myocyte enhancer factor-2c (MEF2c), a transcription factor of GLUT4. In differentiated myoblasts, the expression of GLUT1, GLUT4, and MEF2c mRNAs was greater in DM cattle than in NM cattle (P < 0.01). In the presence and absence of insulin, glucose uptake in myoblasts was increased in DM cattle relative to that of NM cattle (P < 0.01). The addition of myostatin decreased the expression of GLUT4 and MEF2c mRNAs in DM myoblasts (P < 0.05). Results of the present study suggest that myostatin inhibits the expression of GLUT4 mRNA possibly via MEF2c and that the greater ability of the DM cattle to produce muscle relative to the NM cattle may be due to their greater sensitivity to insulin and greater use of glucose. (キーワード) Animals / Blood Glucose / Cattle / Gene Expression Regulation / Glucose Tolerance Test / Glucose Transporter Type 4 / Insulin / Muscle, Skeletal / Myoblasts / Myostatin / RNA, Messenger (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.domaniend.2014.01.007 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24906930 ● Search Scopus @ Elsevier (PMID): 24906930 ● Search Scopus @ Elsevier (DOI): 10.1016/j.domaniend.2014.01.007 (DOI: 10.1016/j.domaniend.2014.01.007, PubMed: 24906930)
16.	Shunsuke Iwasaki, Masato Miyake, Shinichiro Hayashi, Hitoshi Watanabe, Yuya Nagasawa, Shunsuke Terada, Kouichi Watanabe, Shyuichi Ohwada, Haruki Kitazawa, Michael T. Rose and Hisashi Aso : Effect of myostatin on chemokine expression in regenerating skeletal muscle cells., Cells, Tissues, Organs, Vol.198, No.1, 66-74, 2013. (要約) Transforming growth factor- (TGF-) is implicated in the regulatory expression of chemokines that control multiple steps in myogenesis. However, it remains to be established whether myostatin, a member of the TGF- superfamily, affects chemokine expression in skeletal muscle. We investigated the effects of myostatin on the expression of mRNAs and proteins for 4 chemokines (CXCL1, CXCL2, CXCL6, CCL2) in intact and regenerating musculus longissimus thoracis from normal-muscled (NM) and double-muscled (DM) cattle. These chemokines were expressed in regenerating muscle, and their expression was always lower in DM than in NM cattle. Immunohistochemistry revealed that CXCL1 and CXCL6 were detected in the regenerating areas of myoblasts and myotubes in both NM and DM cattle. In cultures of myoblasts isolated from the regenerating muscles, significantly less CXCL1, CXCL2 and CCL2 mRNA was expressed in DM myoblasts than in NM myoblasts during the proliferating stage (P-stage). The expression of CXCL1, CXCL2 and CCL2 mRNAs in NM myoblasts and CXCL1, CXCL2 and CXCL6 mRNAs in DM myoblasts decreased upon switching from P-stage to fusion stage (F-stage). Also, the expression of CXCL1, CXCL2 and CXCL6 mRNAs was significantly lower in DM than in NM myoblasts during the F-stage. The addition of 100 ng/ml myostatin during the F-stage attenuated the expression of CXCL1 and CXCL2 mRNAs and augmented that of CCL2. These results show for the first time that myostatin regulates the differential expression of chemokines in skeletal muscle cells. (キーワード) Animals / Cattle / Cell Proliferation / Cells, Cultured / Chemokines / Gene Expression Regulation, Developmental / Muscle Development / Muscle, Skeletal / Myoblasts / Myostatin / RNA, Messenger / Regeneration (出版サイトへのリンク) ● Publication site (DOI): 10.1159/000351462 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23838214 ● Search Scopus @ Elsevier (PMID): 23838214 ● Search Scopus @ Elsevier (DOI): 10.1159/000351462 (DOI: 10.1159/000351462, PubMed: 23838214)
17.	Shunsuke Iwasaki, Masato Miyake, Hitoshi Watanabe, Eri Kitagawa, Kouichi Watanabe, Shyuichi Ohwada, Haruki Kitazawa, Michael T. Rose and Hisashi Aso : Expression of myostatin in neural cells of the olfactory system., Molecular Neurobiology, Vol.47, No.1, 1-8, 2012. (要約) Recent studies show that myostatin mRNA expression is found in some regions of the brain. However, the functional significance of this is currently unknown. We therefore investigated myostatin expression and function in the brain. In this study, we used immunohistochemistry, in situ hybridization, and RT-PCR analysis to reveal that myostatin is expressed in the mitral cells in the olfactory bulb (OB) and in neurons in the olfactory cortex (OC). Using 3D reconstruction, mitral cells positive for myostatin were positioned in the lateral and ventral regions of the OB. In contrast, myostatin-positive mitral cells were detected in mice at 2 weeks of age, but not on days 0 and 7 after birth. Activin receptor IIB, a myostatin receptor, was expressed in the OB, OC, hippocampus, and paraventricular thalamic nucleus. Moreover, c-Fos immunostaining in granule cells in the OB was augmented after intracerebroventricular injection of myostatin. These findings suggest that myostatin is localized in specific cells associated with the olfactory system of the brain and may act as a key inhibitor in cell and/or signal development of the olfactory system. (キーワード) Activin Receptors, Type II / Activins / Animals / Base Sequence / Gene Expression Regulation / Injections, Intraventricular / Mice / Mice, Inbred C57BL / Molecular Sequence Data / Myostatin / Neurons / Olfactory Bulb / Olfactory Pathways / Protein Transport / Proto-Oncogene Proteins c-fos / RNA, Messenger / Reproducibility of Results (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s12035-012-8342-1 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22941030 ● Search Scopus @ Elsevier (PMID): 22941030 ● Search Scopus @ Elsevier (DOI): 10.1007/s12035-012-8342-1 (DOI: 10.1007/s12035-012-8342-1, PubMed: 22941030)
18.	Masato Miyake, Hideyuki Takahashi, Eri Kitagawa, Hitoshi Watanabe, Takahiro Sakurada, Hisashi Aso and Takahiro Yamaguchi : AMPK activation by AICAR inhibits myogenic differentiation and myostatin expression in cattle., Cell and Tissue Research, Vol.349, No.2, 615-623, 2012. (要約) AMP-activated protein kinase (AMPK) regulates metabolism in skeletal muscle, and myostatin (MSTN) negatively regulates skeletal muscle development and growth. In the present study, AMPK activation and the relationship between AMPK and MSTN during myogenic differentiation were investigated in cultures derived from bovine skeletal muscle. Myoblasts capable of forming myotubes were obtained from bovine skeletal muscle and treated with AICAR to activate AMPK, resulting in suppressed myotube formation. AICAR treatment significantly reduced the expression of MSTN mRNA during myogenic differentiation. Combined treatment with AICAR and MSTN suppressed myotube formation to a greater extent than AICAR alone. SB431542, an inhibitor of MSTN signaling, promoted myotube formation during myogenic differentiation. However, simultaneous treatment with AICAR blocked this effect of SB431542. Therefore, AMPK activation inhibits myogenic differentiation but may suppress MSTN expression to balance muscle development. (キーワード) AMP-Activated Protein Kinases / Aminoimidazole Carboxamide / Animals / Cattle / Cell Culture Techniques / Cell Differentiation / Down-Regulation / Enzyme Activation / Male / Muscle Fibers, Skeletal / Myoblasts / Myostatin / RNA, Messenger / Ribonucleotides (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s00441-012-1422-8 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22622802 ● Search Scopus @ Elsevier (PMID): 22622802 ● Search Scopus @ Elsevier (DOI): 10.1007/s00441-012-1422-8 (DOI: 10.1007/s00441-012-1422-8, PubMed: 22622802)
19.	Masato Miyake, Shinichiro Hayashi, Shunsuke Iwasaki, Takafumi Uchida, Kouichi Watanabe, Shyuichi Ohwada, Hisashi Aso and Takahiro Yamaguchi : TIEG1 negatively controls the myoblast pool indispensable for fusion during myogenic differentiation of C2C12 cells., Journal of Cellular Physiology, Vol.226, No.4, 1128-1136, 2011. (要約) The transforming growth factor (TGF)-β inducible early gene (TIEG)-1 is implicated in the control of cell proliferation, differentiation, and apoptosis in some cell types. Since TIEG1 functioning may be associated with TGF-β, a suppressor of myogenesis, TIEG1 is also likely to be involved in myogenesis. Therefore, we investigated the function of TIEG1 during myogenic differentiation in vitro using the murine myoblasts cell line, C2C12. TIEG1 expression increased during differentiation of C2C12 cells. Constitutive expression of TIEG1 reduced survival and decreased myotube formation. Conversely, knocking down TIEG1 expression increased the number of viable cells during differentiation, and accelerated myoblast fusion into multinucleated myotubes. However, expression of the myogenic differentiation marker, myogenin, remained unaffected by TIEG1 knockdown. The mechanism underlying these events was investigated by focusing on the regulation of myoblast numbers after induction of differentiation. The knockdown of TIEG1 led to changes in cell cycle status and inhibition of apoptosis during the initial stages of differentiation. Microarray and real-time PCR analyses showed that the regulators of cell cycle progression were highly expressed in TIEG1 knockdown cells. Therefore, TIEG1 is a negative regulator of the myoblast pool that causes inhibition of myotube formation during myogenic differentiation. (キーワード) Animals / Apoptosis / Cell Count / Cell Cycle / Cell Cycle Proteins / Cell Differentiation / Cell Fusion / Cell Line / DNA-Binding Proteins / Gene Knockdown Techniques / Mice / Muscle Development / Muscle Fibers, Skeletal / Myoblasts / Myogenin / Transcription Factors / Up-Regulation (出版サイトへのリンク) ● Publication site (DOI): 10.1002/jcp.22434 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20945337 ● Search Scopus @ Elsevier (PMID): 20945337 ● Search Scopus @ Elsevier (DOI): 10.1002/jcp.22434 (DOI: 10.1002/jcp.22434, PubMed: 20945337)
20.	Hitoshi Watanabe, Daisuke Akasaka, Hideki Ogasawara, Kan Sato, Masato Miyake, Kazuki Saito, Yu Takahashi, Takashi Kanaya, Ikuro Takakura, Tetsuya Hondo, Guozheng Chao, T Michael Rose, Shyuichi Ohwada, Kouichi Watanabe, Takahiro Yamaguchi and Hisashi Aso : Peripheral serotonin enhances lipid metabolism by accelerating bile acid turnover., Endocrinology, Vol.151, No.10, 4776-4786, 2010. (要約) Serotonin is synthesized by two distinct tryptophan hydroxylases, one in the brain and one in the periphery. The latter is known to be unable to cross the blood-brain barrier. These two serotonin systems have apparently independent functions, although the functions of peripheral serotonin have yet to be fully elucidated. In this study, we have investigated the physiological effect of peripheral serotonin on the concentrations of metabolites in the circulation and in the liver. After fasting, mice were ip injected with 1 mg serotonin. The plasma glucose concentration was significantly elevated between 60 and 270 min after the injection. In contrast, plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations were decreased. The hepatic glycogen synthesis and concentrations were significantly higher at 240 min. At the same time, the hepatic triglyceride content was significantly lower than the basal levels noted before the serotonin injection, whereas the hepatic cholesterol content was significantly higher by 60 min after the injection. Furthermore, serotonin stimulated the contraction of the gallbladder and the excretion of bile. After the serotonin injection, there was a significant induction of apical sodium-dependent bile acid transporter expression, resulting in a decrease in the concentration of bile acids in the feces. Additionally, data are presented to show that the functions of serotonin are mediated through diverse serotonin receptor subtypes. These data indicate that peripheral serotonin accelerates the metabolism of lipid by increasing the concentration of bile acids in circulation. (キーワード) Animals / Bile Acids and Salts / Dose-Response Relationship, Drug / Fasting / Gallbladder / Glucose / Glycogen / Ileum / Injections, Intraperitoneal / Insulin / Lipid Metabolism / Liver / Male / Mice / Mice, Inbred C57BL / Serotonin (出版サイトへのリンク) ● Publication site (DOI): 10.1210/en.2009-1349 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20685881 ● Search Scopus @ Elsevier (PMID): 20685881 ● Search Scopus @ Elsevier (DOI): 10.1210/en.2009-1349 (DOI: 10.1210/en.2009-1349, PubMed: 20685881)
21.	Masato Miyake, Shinichiro Hayashi, Yoshikazu Taketa, Shunsuke Iwasaki, Kouichi Watanabe, Shyuich Ohwada, Hisashi Aso and Takahiro Yamaguchi : Myostatin down-regulates the IGF-2 expression via ALK-Smad signaling during myogenesis in cattle., Animal Science Journal, Vol.81, No.2, 223-229, 2010. (要約) Myostatin (MSTN) is a negative regulator during muscle differentiation, whereas insulin-like growth factors (IGFs) are essential for muscle development. MSTN and IGFs act oppositely during myogenesis, but there is little information on the mutual relationship of MSTN and IGFs. The present study was conducted to examine whether MSTN affects IGF expression during early myogenesis in cattle. IGF-1 mRNA was similarly expressed in M. longissimus thoracis of double-muscled (DM) and normal (NM) Japanese shorthorn cattle. IGF-2 mRNA expression was consistently higher in the normal and regenerating muscle of DM cattle than those of NM cattle. When myoblasts were isolated from regenerating M. longissimus thoracis, IGF-2 mRNA expression showed a significant increase in differentiating DM derived myoblasts (DM-myoblasts) as compared with differentiating NM derived myoblasts (NM-myoblasts). An addition of recombinant mouse myostatin (rMSTN) to myoblast cultures attenuated IGF-2 mRNA expression and decreased myotube formation, but did not effect IGF-1 mRNA expression. An activin-like kinase (ALK) inhibitor, SB431542, mediates MSTN action, suppressed the translocation of Smad2/3 into the nucleus in DM-myoblasts, and restored the attenuated IGF-2 mRNA expression and the decreased myotube formation induced by rMSTN in myoblast cultures. The findings indicate that MSTN may negatively regulate myoblast differentiation by suppressing IGF-2 expression via ALK-Smad signaling. (キーワード) Activin Receptors / Animals / Cattle / Down-Regulation / Insulin-Like Growth Factor II / Muscle Development / Myostatin / Signal Transduction / Smad Proteins (出版サイトへのリンク) ● Publication site (DOI): 10.1111/j.1740-0929.2009.00725.x (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20438504 ● Search Scopus @ Elsevier (PMID): 20438504 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1740-0929.2009.00725.x (DOI: 10.1111/j.1740-0929.2009.00725.x, PubMed: 20438504)
22.	Masato Miyake, Shinichiro Hayashi, Shunsuke Iwasaki, Guozheng Chao, Hideyuki Takahashi, Kouichi Watanabe, Shyuichi Ohwada, Hisashi Aso and Takahiro Yamaguchi : Possible role of TIEG1 as a feedback regulator of myostatin and TGF-beta in myoblasts., Biochemical and Biophysical Research Communications, Vol.393, No.4, 762-766, 2010. (要約) Myostatin and TGF-beta negatively regulate skeletal muscle development and growth. Both factors signal through the Smad2/3 pathway. However, the regulatory mechanism of myostatin and TGF-beta signaling remains unclear. TGF-beta inducible early gene (TIEG) 1 is highly expressed in skeletal muscle and has been implicated in the modulation of TGF-beta signaling. These findings prompted us to investigate the effect of TIEG1 on myostatin and TGF-beta signaling using C2C12 myoblasts. Myostatin and TGF-beta induced the expression of TIEG1 and Smad7 mRNAs, but not TIEG2 mRNA, in proliferating C2C12 cells. When differentiating C2C12 myoblasts were stimulated by myostatin, TIEG1 mRNA was up-regulated at a late stage of differentiation. In contrast, TGF-beta enhanced TIEG1 expression at an early stage. Overexpression of TIEG1 prevented the transcriptional activation of Smad by myostatin and TGF-beta in both proliferating or differentiating C2C12 cells, but the expression of Smad2 and Smad7 mRNAs was not affected. Forced expression of TIEG1 inhibited myogenic differentiation but did not cause more inhibition than the empty vector in the presence of myostatin or TGF-beta. These results demonstrate that TIEG1 is one possible feedback regulator of myostatin and TGF-beta that prevents excess action in myoblasts. (キーワード) Animals / Cell Line / DNA-Binding Proteins / Feedback, Physiological / Mice / Muscle Development / Myoblasts / Myostatin / Signal Transduction / Smad Proteins / Transcription Factors / Transforming Growth Factor beta (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.bbrc.2010.02.077 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20171187 ● Search Scopus @ Elsevier (PMID): 20171187 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2010.02.077 (DOI: 10.1016/j.bbrc.2010.02.077, PubMed: 20171187)
23.	Susumu Muroya, Kouichi Watanabe, Shinichiro Hayashi, Masato Miyake, Shigeru Konashi, Youichi Sato, Manabu Takahashi, Shigeki Kawahata, Yoshisato Yoshikawa, Hisashi Aso, Koichi Chikuni and Takahiro Yamaguchi : Muscle type-specific effect of myostatin deficiency on myogenic regulatory factor expression in adult double-muscled Japanese Shorthorn cattle., Animal Science Journal, Vol.80, No.6, 678-685, 2009. (要約) To clarify muscle type-specific effect of myostatin on myogenic regulatory factors (MRFs), we examined mRNA expression of MRFs in five skeletal muscles of normal (NM) and myostatin-deficient double-muscled (DM) adult Japanese Shorthorn cattle by quantitative reverse-transcribed PCR. Among the four MRFs, namely, Myf5, MyoD, myogenin, and MRF4, MyoD expression was different among the muscles of the DM cattle (P < 0.01) but not of the NM cattle. Meanwhile, MyoD expression was significantly elevated only in masseter (MS) muscle in the DM cattle due to the myostatin deficiency (P < 0.05). Myf5 and MRF4 expression in semitendinosus (ST) was higher in the DM than in the NM cattle (P < 0.05). According to analysis of myosin heavy chain (MyHC) isoform expression, more MyHC-2x and -2a and less -slow isoforms were expressed in the longissimus and ST muscles compared to the MS muscle in both cattle (P < 0.05), but no significant difference in MyHC expression was observed between the NM and DM cattle. Taken together, myostatin has influences on Myf5 and MRF4 expression in faster-type muscles and on MyoD expression in slower-type muscles, suggesting a possible muscle type-specific effect of myostatin in skeletal muscle growth and maintenance. (キーワード) Animals / Cattle / Muscle, Skeletal / Myogenic Regulatory Factors / Myostatin (出版サイトへのリンク) ● Publication site (DOI): 10.1111/j.1740-0929.2009.00684.x (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20163658 ● Search Scopus @ Elsevier (PMID): 20163658 ● Search Scopus @ Elsevier (DOI): 10.1111/j.1740-0929.2009.00684.x (DOI: 10.1111/j.1740-0929.2009.00684.x, PubMed: 20163658)
24.	Yasuhiro Nagai, Hideki Ogasawara, Yoshikazu Taketa, Hisashi Aso, Takashi Kanaya, Masato Miyake, Kouichi Watanabe, Shyuichi Ohwada, Yoshihiro Muneta and Takahiro Yamaguchi : Expression of inflammatory-related factors in porcine anterior pituitary-derived cell line., Veterinary Immunology and Immunopathology, Vol.124, No.3-4, 201-208, 2008. (要約) Recent studies have shown that undifferentiated stem cells act as immunomodulators. To investigate the immunomodulatory function of the progenitor cells of the anterior pituitary gland, we attempted to establish a stem/progenitor cell line from the porcine anterior pituitary gland, and to detail its inflammatory cytokine expression. A cloned cell line from the porcine anterior pituitary gland was established and was designated as the porcine anterior pituitary-derived cell line (PAPC). PAPC expressed the mRNA of Nanog and Oct-4, and showed positive immunoreactivity for beta-catenin and Hes1 in its nucleus. PAPC grew stably by repeated passage and rapidly in the EGF and bFGF containing medium. RT-PCR showed that PAPC expressed mRNA of IL-1alpha, IL-6, IL-12, IL-15, IL-18 and TLR4. PAPC expressed S100alpha and IL-18 protein, which was localized in the marginal epithelial cells of Rathke's pouch. These results suggest that PAPC is a stem/progenitor cell and may regulate anterior pituitary cell function through an immuno-endocrine pathway. (キーワード) Animals / Cytokines / Female / Immunohistochemistry / Inflammation / Pituitary Gland, Anterior / RNA, Messenger / Reverse Transcriptase Polymerase Chain Reaction / Stem Cells / Swine (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.vetimm.2008.03.007 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18440649 ● Search Scopus @ Elsevier (PMID): 18440649 ● Search Scopus @ Elsevier (DOI): 10.1016/j.vetimm.2008.03.007 (DOI: 10.1016/j.vetimm.2008.03.007, PubMed: 18440649)
25.	Shinichiro Hayashi, Masato Miyake, Kouichi Watanabe, Hisashi Aso, Seigo Hayashi, Shyuichi Ohwada and Takahiro Yamaguchi : Myostatin preferentially down-regulates the expression of fast 2x myosin heavy chain in cattle., Proceedings of the Japan Academy. Series B, Physical and biological sciences, Vol.84, No.8, 354-362, 2008. (要約) Myostatin is involved in an inhibitor of muscular growth and differentiation. Myoblasts derived from double-muscled Japanese shorthorn cattle (DM myoblasts) with absence of functional myostatin had higher abilities to proliferate and differentiate than myoblasts derived from normal-muscled cattle (NM myoblasts). In DM myoblasts, mRNA expressions of fetal myosin heavy chain (MyHC) in growth medium and of fast 2a and 2x MyHC in fusion medium were significantly greater than that in NM myoblasts. No significant difference existed in expressions of embryonic and slow MyHC mRNA between DM and NM myoblasts. The expression of MyoD mRNA was suppressed in myoblasts by administration of myostatin. Two cloned DM myoblast strains (DMc) were established. Addition of myostatin for DMc resulted in less myotube formation and suppression of mRNA expression of fast 2x MyHC. These findings suggest that the endogenous myostatin preferentially down-regulates the expression of the fast 2x MyHC and participates in differentiation of myofiber types during early bovine myogenesis. (キーワード) Animals / Cattle / Cells, Cultured / Down-Regulation / Muscle, Skeletal / Myosin Heavy Chains / Myostatin / RNA, Messenger / Transforming Growth Factor beta (出版サイトへのリンク) ● Publication site (DOI): 10.2183/pjab.84.354 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18941308 ● Search Scopus @ Elsevier (PMID): 18941308 ● Search Scopus @ Elsevier (DOI): 10.2183/pjab.84.354 (DOI: 10.2183/pjab.84.354, PubMed: 18941308)
26.	Masato Miyake, Shinichiro Hayashi, Tomomi Sato, Yoshikazu Taketa, Kouichi Watanabe, Shinji Hayashi, Sachi Tanaka, Shyuichi Ohwada, Hisashi Aso and Takahiro Yamaguchi : Myostatin and MyoD family expression in skeletal muscle of IGF-1 knockout mice., Cell Biology International, Vol.31, No.10, 1274-1279, 2007. (要約) Insulin-like growth factor-1 (IGF-1) is a positive regulator in proliferation and differentiation of skeletal muscle cells, while myostatin (MSTN) is a member of transforming growth factor beta superfamily that acts as a negative regulator of skeletal muscle mass. The present study was performed to detail whether a correlation exists between MSTN and IGF-1 in skeletal muscle of IGF-1 knockout mice (IGF-1(-/-)) and their wild type (WT; i.e., IGF-1(+/+)) littermates. The body weight of IGF-1(-/-) animals was 32% that of WT littermates. The fiber cross-sectional areas (CSA) and number of fibers in M. rectus femoris of IGF-1(-/-) animals were 49 and 59% those of WT animals, respectively. Thus, muscle hypoplasia of IGF-1(-/-) undoubtedly was confirmed. Myostatin mRNA levels and protein levels were similar between M. gastrocnemius of IGF-1(-/-) and WT animals. Myostatin immunoreactivity was similarly localized in muscle fibers of both IGF-1(-/-) and WT M. rectus femoris. The mRNA levels of MyoD family (Myf5, MyoD, MRF4, myogenin) were differentially expressed in IGF-1(-/-)M. gastrocnemius, in which the mRNA expression of MRF4 and myogenin was significantly lower, whereas there were no changes in the mRNA expression of Myf5 and MyoD. These findings first describe that myostatin expression is not influenced by intrinsic failure of IGF-1, although MRF4 and myogenin are downregulated. (キーワード) Animals / Insulin-Like Growth Factor I / Male / Mice / Mice, Knockout / Muscle Strength / Muscle, Skeletal / MyoD Protein / Myogenic Regulatory Factor 5 / Myogenic Regulatory Factors / Myogenin / Myostatin / RNA, Messenger / Reverse Transcriptase Polymerase Chain Reaction / Transforming Growth Factor beta (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.cellbi.2007.05.007 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17590360 ● Search Scopus @ Elsevier (PMID): 17590360 ● Search Scopus @ Elsevier (DOI): 10.1016/j.cellbi.2007.05.007 (DOI: 10.1016/j.cellbi.2007.05.007, PubMed: 17590360)

総説・解説:

1.	三宅雅人, 親泊政一 : 小胞体ストレス応答を介した臓器関連による代謝制御機構, Clinical Calcium, Vol.28, No.11, 1548-1553, 2018年10月. (要約) Organs do not independently coordinate their metabolic activity:close communication between different organ systems is essential to regulate metabolism effectively. In recent years, the unfolded protein response(UPR), which is an adaptive mechanism to decrease the amount of unfolded or misfolded proteins in the ER, has been found to regulate metabolic function not only at the cellular level but also at the whole-organism level by way of inter-organ communications. This manuscript will present the most recent findings on the role of the UPR in inter-organ metabolic networks. (キーワード) 小胞体 (endoplasmic reticulum) / Humans / Metabolic Networks and Pathways / Proteins / Unfolded Protein Response (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30374012 ● Search Scopus @ Elsevier (PMID): 30374012 (PubMed: 30374012)
2.	親泊政一, 三宅雅人 : マイオカインによる代謝調節, 日本臨牀増刊号, Vol.74, No.1, 179-183, 2016年2月.
3.	佐藤亮祐, 三宅雅人, 倉橋清衛, 高原一菜, 野村明利, 津川和江, 小倉淳, 安井夏生, 親泊政一 : 小胞体ストレス伝達蛋白質ATF4βは成長軟骨細胞の機能成熟に重要である, Pharma Medica, Vol.31, No.2, 163, 2013年2月.
4.	三宅雅人, 野村明利, 高原一菜, 小倉淳, 佐藤亮祐, 倉橋清衛, 親泊美帆, 井上寛, 親泊政一 : 骨格筋での小胞体ストレスなどからのeIF2αリン酸化によるエネルギー消費の制御と抗肥満作用, Pharma Medica, Vol.31, No.2, 161, 2013年2月.

国際会議:

1.	北風圭介, 親泊美帆, 張君, 津川和江, 河野恵理, 三宅雅人, 竹之内康広, 坪井一人, 岡本安雄, 親泊政一 : 膵β細胞における小胞体ストレス応答転写因子ATF4の機能解明, 第61回日本生化学会中国・四国支部例会, 誌上開催, 2020年6月.
2.	Masato Miyake, Zhang Jun and Seiichi Oyadomari : Preemptive activation of integrated stress responses in adipose tissue suppresses food intake and improves obesity through growth and differentiation factor 15, EMBO workshop, Nov. 2019.
3.	Akira Izutani, Yuji Furumoto, Yoshimasa Hamada, Masato Miyake, Kenji Teranishi, Naoyuki Shimomura and Seiichi Oyadomari : The Influence of Applying High Electrical Field Pulses on Unfolded Protein Response of cells, The 2019 IEEE Pulsed Power and Plasma Science Conference, 4-pages, Orlando, Jun. 2019.
4.	Keisuke Kitakaze, Kiyoe Kurahashi, Masato Miyake, Yoshimasa Hamada, Miho Oyadomari and Seiichi Oyadomari : Targeted Deletion of ATF4 in β-cells Leads to the Vulnerability and Dedifferentiation During ER Stress, American Diabetes Association 78th scientific sessions, Jun. 2018.
5.	Yuji Furumoto, Daiki Sato, Yoshifumi Hamada, Masato Miyake, Kenji Teranishi, Naoyuki Shimomura and Seiichi Oyadomari : Activation of Endoplasmic Reticulum Stress Response by Applying of Nanosecond Pulsed Electric Fields for Medical Application, Proceedings of the 2018 IEEE International Power Modulator and High Voltage Conference, 456-460, Jackson, Jun. 2018. (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-85077809992 (Elsevier: Scopus)
6.	Masatoshi Morimoto, Fumitake Tezuka, Fumio Hayashi, Kazuta Yamashita, Yoichiro Takata, Toshinori Sakai, Kousaku Higashino, Akihiro Nagamachi, Koichi Sairyo, Ryosuke Sato, Masato Miyake and Seiichi Oyadomari : ER STRESS AGGRAVATES THE HYPERTROPHY OF THE LIGAMNTUM FLAVUM, International Society for the Study of Lumbar Spine(ISSLS) 2017( May 29June 2, 2017), Athens, May 2017.
7.	Kiyoe Kurahashi, 森智子, 宮本千伸, 津川和江, Miho Oyadomari, Kazuna Takahara, 木村千寿子, Masato Miyake, Toshio Matsumoto and Seiichi Oyadomari : Saturated Fatty Acids Predominantly Activate PERK Pathway via Altered Composition of the Endoplasmic Reticulum Membrane, and Reduce Insulin Secretion in Pancreatic Cell by Translation Attenuation, 75th ADA scientific sessions, Jun. 2015.
8.	Hiroshi Fukuda, Masato Miyake, Hiroto Hirai, Kenji Teranishi, Naoyuki Shimomura and Seiichi Oyadomari : Effects on Endoplasmic Reticulum Stress Response of Applying Nanosecond Pulsed Electric Fields, Digest of Technical Papers-IEEE International Pulsed Power Conference, 370-373, Austin, Jun. 2015. (出版サイトへのリンク) ● Publication site (DOI): 10.1109/PPC.2015.7296943 (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.1109/PPC.2015.7296943 (DOI: 10.1109/PPC.2015.7296943)
9.	Masato Miyake, Kiyoe Kurahashi and Seiichi Oyadomari : Identification and Characterization of a Small-molecule Inducer of ATF4 for Promoting Insulin Synthesis in Pancreatic cells, 74th ADA Scientific Sessions, Jun. 2014.
10.	Hiroto Hirai, Masato Miyake, Akihiko Nagano, Kenji Teranishi, Naoyuki Shimomura and Seiichi Oyadomari : Investigation About Effects on Endoplasmic Reticulum Stress Responses by Applying Nanosecond Pulsed Electricfields, Proceedings of the 2014 IEEE International Power Modulator and High Voltage Conference, 419-422, Santa Fe, Jun. 2014. (出版サイトへのリンク) ● Publication site (DOI): 10.1109/IPMHVC.2014.7287300 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-84947087754 (DOI: 10.1109/IPMHVC.2014.7287300, Elsevier: Scopus)
11.	Nomura Akitoshi, Masato Miyake, Atsushi Ogura, Kiyoe Kurahashi, Mori Tomoko, Tsugawa Kazue, Miyamoto Chinobu, Miho Oyadomari and Seiichi Oyadomari : Role of the PERK signaling pathway in metabolic process, International Symposium Hannover-Tokushima Research Communication, Aug. 2013.
12.	Masato Miyake, NOMURA AKITOSHI, Atsushi Ogura, Kazuna Takahara, Kiyoe Kurahashi, Ryosuke Sato, Miho Oyadomari, Hiroshi Inoue and Seiichi Oyadomari : Phosphorylation of eIF2 in skeletal muscle increases energy expenditure and are resistant to diet induced obesity., The American Diabetes Association's 73nd Scientific Sessions, Jul. 2013.

国内講演発表:

1.	北風圭介, 親泊美帆, 張君, 津川和江, 河野恵理, 三宅雅人, 竹之内康広, 坪井一人, 岡本安雄, 親泊政一 : 小胞体ストレス応答転写因子ATF4の機能不全は膵β細胞の脱分化を惹起する, 第93回日本生化学会大会, 2022年9月.
2.	三宅雅人, 傍島光昭, 倉橋清衛, 重永章, 傳田将也, 大髙章, 齋尾智英, 小迫英尊, 親泊政一 : 膵β細胞において小胞体ストレスを軽減しインスリン合成を促進する新規化合物の同定, 第66回日本糖尿病学会年次学術集会, 2022年5月.
3.	傍島光昭, 三宅雅人, 井上亮太, 白川純, 有馬寛, 親泊政一 : グルコース応答性インスリン分泌制御における転写因子ATF4の多面的な役割, 第32回分子糖尿病学シンポジウム, 2021年12月.
4.	寺奥大貴, 齋藤裕, 池本哲也, 宮崎克己, 山田眞一郎, 森根裕二, 三宅雅人, 親泊政一, 島田光生 : ヒト脂肪由来間葉系幹細胞を基にした機能的肝細胞様細胞の分化誘導, 第57回日本移植学会総会, 2021年9月.
5.	齋藤裕, 池本哲也, 宮崎克己, 徳田和憲, 山田眞一郎, 居村暁, 森根裕二, 三宅雅人, 親泊政一, 島田光生 : ヒト脂肪由来間葉系幹細胞から肝細胞様細胞の創出-肝不全・代謝性肝疾患に対する肝移植から細胞治療へ-, 第263回徳島医学会学術集会(令和3年度夏期), 2021年8月.
6.	齋藤裕, 池本哲也, 宮崎克己, 徳田和憲, 山田眞一郎, 居村暁, 森根裕二, 三宅雅人, 親泊政一, 島田光生 : ヒト脂肪由来間葉系幹細胞から肝細胞様細胞の創出, 第20回日本再生医療学会総会, 2021年3月.
7.	齋藤裕, 池本哲也, 宮崎克己, 徳田和憲, 山田眞一郎, 居村暁, 森根裕二, 三宅雅人, 親泊政一, 島田光生 : ヒト脂肪由来間葉系幹細胞から肝細胞様細胞の創出- 肝不全・代謝性肝疾患に対する肝移植から細胞治療へ -, 第262回徳島医学会学術集会, 2021年3月.
8.	宮崎克己, 齋藤裕, 高露萍, 池本哲也, 山田眞一郎, 居村暁, 森根裕二, 三宅雅人, 親泊政一, 島田光生 : ヒト脂肪由来間葉系幹細胞から分化誘導した肝細胞様細胞の遺伝子発現解析, 第56回日本移植学会総会, 2020年11月.
9.	三宅雅人, 親泊政一 : 小胞体ストレス応答による細自立的・非自立的代謝制御, 第93 回日本生化学会大, 2020年9月.
10.	北風圭介, 谷内秀輔, 河野恵理, 濱田良真, 三宅雅人, 親泊美帆, 小島宏建, 小迫英尊, 栗原ともこ, 吉田優, 細谷孝充, 親泊政一 : 小胞体ストレス下のタンパク質凝集と細胞毒性を緩和する化学シャペロンの同定, 第93回日本薬理学会年会, 2020年3月.
11.	谷内秀輔, 小迫英尊, 三宅雅人, 親泊美帆, 親泊政一 : 小胞体ストレスセンサーPERK による炎症性メディエーター調節機構, 第14回小胞体ストレス研究会, 2019年9月.
12.	北風圭介, 谷内秀輔, 河野恵理, 濱田良真, 三宅雅人, 親泊美帆, 小島宏達, 小迫英尊, 栗原ともこ, 吉田優, 細谷孝充, 親泊政一 : 小胞体ストレス下のタンパク質凝集を標的とする新規化学シャペロンの同定, 第92回日本生化学会大会, 2019年9月.
13.	北風圭介, 谷内秀輔, 河野恵理, 濱田良真, 三宅雅人, 親泊美帆, 小島宏達, 小迫英尊, 栗原ともこ, 吉田優, 細谷孝充, 親泊政一 : プロテオパチーの治療薬創出を目指した新規化学シャペロンの探索, 第31回創薬・薬理フォーラム岡山, 2019年7月.
14.	北風圭介, 谷内秀輔, 河野恵理, 濱田良真, 三宅雅人, 親泊美帆, 小島宏達, 小迫英尊, 栗原ともこ, 吉田優, 細谷孝充, 親泊政一 : 小胞体におけるタンパク質凝集と細胞毒性を軽減する新規化学シャペロンの同定, 第60回日本生化学中国・四国支部例会, 2019年5月.
15.	三宅雅人, 親泊政一 : 脂肪細胞におけるストレス応答性転写因子ATF4の機能解明, 第30回分子糖尿病学シンポジウム, 2018年12月.
16.	谷内秀輔, 小迫英尊, 三宅雅人, 親泊美帆, 親泊政一 : HMGB1とHMGB2はPERKの新規リン酸化基質である, 第13回小胞体ストレス研究会, 2018年11月.
17.	山川哲生, 三宅雅人, 森本雅俊, 久永哲, 倉橋清衛, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : ERK経路下流因子ncRNAによる癌増殖機構の解析, 第13回小胞体ストレス研究会, 2018年11月.
18.	張君, 三宅雅人, 津川和江, 親泊美帆, 親泊政一 : セリン710残基によるIRE1α-RNase 活性の制御, 第13回小胞体ストレス研究会, 2018年11月.
19.	北風圭介, 谷内秀輔, 河野恵理, 濱田良真, 三宅雅人, 親泊美帆, 小島宏達, 小迫英尊, 栗原ともこ, 吉田優, 細谷孝充, 親泊政一 : 細胞ベースのハイスループットスクリーニングによる新規化学シャペロンの同定, 第13回小胞体ストレス研究会, 2018年11月.
20.	三宅雅人, 谷内秀輔, 親泊政一 : CRISPRスクリーンで同定した新規PERK経路制御因子の機能解明, 第13回小胞体ストレス研究会, 2018年11月.
21.	濱田良真, 古元雄二, 泉谷亮, 北風圭介, 谷内秀輔, 三宅雅人, 親泊美帆, 寺西研二, 下村直行, 親泊政一 : 薬理・物理的なeIF2αのリン酸化誘導とキナーゼの同定, 第13回小胞体ストレス研究会, 2018年11月.
22.	三宅雅人, 張君, 親泊政一 : 脂肪組織での統合的ストレス応答はDdit3-Gdf15経路による摂食抑制を介して肥満を改善する, 第39回肥満学会, 2018年10月.
23.	三宅雅人, 張君, 久永哲, 親泊美帆, 親泊政一 : 脂肪細胞における統合的ストレス応答は GDF15 を介した摂食抑制により食事性肥満を改善する, 第61回日本糖尿病学会年次学術集会, 2018年5月.
24.	三宅雅人, 親泊政一 : 小胞体ストレス応答因子PERKによる代謝調節機構, ConBio2017(第41回日本分子生物学会年会，第91回日本生化学会大会), 2017年12月.
25.	北風圭介, 三宅雅人, 森本雅俊, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : ATF4 ノックアウトマウスの膵β細胞は小胞体ストレスに脆弱で脱分化をきたす, 第29回分子糖尿病学シンポジウム, 2017年12月.
26.	北風圭介, 三宅雅人, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : 膵β細胞特異的Atf4ノックアウトマウスは小胞体ストレスを介した糖尿病が重症化する, 第12回小胞体ストレス研究会, 2017年10月.
27.	谷内秀輔, 三宅雅人, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : eIF2αのリン酸化はミトコンドリアの代謝機能に関与する, 第12回小胞体ストレス研究会, 2017年10月.
28.	張君, 三宅雅人, 倉橋清衛, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : 高血糖に伴うIRE1のO-GlcNAc修飾は小胞体ストレス応答を減弱させる, 第12回小胞体ストレス研究会, 2017年10月.
29.	山川哲生, 森本雅俊, 久永哲, 三宅雅人, 倉橋清衛, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : 新規PERK経路下流因子Snhg12ホモ欠損マウス解析, 第12回小胞体ストレス研究会, 2017年10月.
30.	久永哲, 三宅雅人, 谷内秀輔, 森本雅俊, 親泊美帆, 親泊政一 : PERK経路の活性化が軟骨細胞のECM分泌に与える影響, 第12回小胞体ストレス研究会, 2017年10月.
31.	森本雅俊, 三宅雅人, 久永哲, 谷内秀輔, 張君, 西良浩一, 親泊政一 : 黄色靭帯肥厚における小胞体ストレスの役割, 第12回小胞体ストレス研究会, 2017年10月.
32.	三宅雅人, 谷内秀輔, 久永哲, 親泊美帆, 親泊政一 : CRISPRライブラリーを用いた新規小胞体ストレス応答制御因子の同定, 第12回小胞体ストレス研究会, 2017年10月.
33.	張君, 三宅雅人, 倉橋清衛, 宮本千伸, 津川和江, 尾野雅哉, 親泊美帆, 親泊政一 : 高血糖に伴うIRE1のO-GlcNAc修飾は小胞体ストレス応答を減弱させる, 第60回日本糖尿病学会年次学術集会, 2017年5月.
34.	張君, 三宅雅人, 津川和江, 宮本千伸, 親泊政一 : UPR欠損マウス胎児線維芽細胞は小胞体からのCa2+放出を介してアポトーシスを誘導する, 第11回臨床ストレス応答学会大会, 2016年11月.
35.	谷内秀輔, 三宅雅人, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : 哺乳類ミトコンドリアUPR は統合的ストレス応答を介さずに誘導される, 第11回小胞体ストレス研究会, 2016年10月.
36.	山川哲生, 三宅雅人, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : 腎癌の予後に関係する新規PERK 経路下流因⼦(ncRNA)について, 第11回小胞体ストレス研究会, 2016年10月.
37.	三宅雅人, 親泊政一 : 脂肪細胞におけるPERK 経路を起点とした細胞間相互作⽤による細胞死の誘導, 第11回小胞体ストレス研究会, 2016年10月.
38.	張君, 三宅雅人, 津川和江, 宮本千伸, 親泊政一 : UPR⽋損マウス胎児線維芽細胞は⼩胞体からのCa2+放出を介してアポトーシスを誘導する, 第11回小胞体ストレス研究会, 2016年10月.
39.	三宅雅人, 張君, 倉橋清衛, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : 脂肪組織での小胞体ストレスなどで活性化されるeIF2αリン酸化シグナルによる肥満抑制作用, 第89回日本生化学会大会, 2016年9月.
40.	倉橋清衛, 河野恵理, 宮本千伸, 津川和江, 親泊美帆, 木村千寿子, 久永哲, 森本雅俊, 山川哲生, 谷内秀輔, 張君, 三宅雅人, 安倍正博, 親泊政一 : ラベルフリー測定によるハイスループットスクリーニングを用いた新規インスリン分泌促進薬の探索, 第59回日本糖尿病学会年次学術集会, 2016年5月.
41.	三宅雅人, 高原一菜, 張君, 倉橋清衛, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : ATF6βの肥満・糖尿病における役割の解明, 第59回日本糖尿病学会年次学術集会, 2016年5月.
42.	三宅雅人, 倉橋清衛, 森智子, 宮本千伸, 津川和江, 三浦恭子, 北原吉朗, 親泊政一 : 小胞体ストレスを減弱させ膵β細胞でのインスリン生合成を促進する新規化合物の同定, 第27回分子糖尿病学シンポジウム, 2015年12月.
43.	谷内秀輔, 三宅雅人, 津川和江, 親泊美帆, 親泊政一 : CRISPR/Cas9システムを用いた統合的ストレス応答を制御するeIF2αキナーゼの検証, 第38回分子生物学会年会・第88回生化学会年会合同大会, 2015年12月.
44.	山川哲生, 小倉淳, 三宅雅人, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : PERK経路の下流因子によって制御される癌細胞増殖機構について, 第38回分子生物学会年会・第88回生化学会年会合同大会, 2015年12月.
45.	三宅雅人, 張君, 志内哲也, 倉橋清衛, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : 小胞体ストレスなどで活性化されるeIF2αリン酸化シグナルによる摂食調節を介した肥満抑制作用, 第38回分子生物学会年会・第88回生化学会年会合同大会, 2015年12月.
46.	張君, 三宅雅人, 倉橋清衛, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : CRISPR/Cas9 を用いた小胞体ストレス応答伝達タンパク質の検証, 第38回分子生物学会年会・第88回生化学会年会合同大会, 2015年12月.
47.	佐藤亮祐, 三宅雅人, 谷内秀輔, 山川哲生, 張君, 倉橋清衛, 森本雅俊, 久永哲, 西良浩一, 親泊政一 : ATF6βは非古典的小胞体ストレス応答として軟骨細胞分化を制御する, 第38回分子生物学会年会・第88回生化学会年会合同大会, 2015年12月.
48.	谷内秀輔, 三宅雅人, 津川和江, 親泊美帆, 親泊政一 : CRISPR/Cas9を用いた統合的ストレス応答に関与するeIF2αキナーゼの解析, 第10回小胞体ストレス研究会, 2015年11月.
49.	張君, 三宅雅人, 倉橋清衛, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : CRISPR/Cas9 を用いた小胞体ストレス応答伝達タンパク質の検証, 第10回小胞体ストレス研究会, 2015年11月.
50.	三宅雅人, 高原一菜, 森本雅俊, 倉橋清衛, 親泊政一 : ATF6βの肥満・糖尿病における役割, 第10回小胞体ストレス研究会, 2015年11月.
51.	森本雅俊, 久永哲, 張君, 谷内秀輔, 山川哲生, 三宅雅人, 西良浩一, 親泊政一 : ATF6αの骨形成における役割, 第10回小胞体ストレス研究会, 2015年11月.
52.	三宅雅人, 倉橋清衛, 森智子, 宮本千伸, 津川和江, 三浦恭子, 北原吉朗, 親泊美帆, 親泊政一 : 小胞体ストレスを標的とした膵β細胞でのインスリン生合成を促進する新規化合物の同定, 第10回臨床ストレス応答学会大会, 2015年11月.
53.	三宅雅人, 張君, 倉橋清衛, 宮本千伸, 津川和江, 親泊美帆, 親泊政一 : 小胞体ストレスなどで活性化されるeIF2αリン酸化シグナルによる摂食調節を介した肥満抑制作用, 第58回日本糖尿病学会年次学術集会, 2015年5月.
54.	倉橋清衛, 森智子, 宮本千伸, 津川和江, 親泊美帆, 高原一菜, 木村千寿子, 三宅雅人, 松本俊夫, 親泊政一 : 膵β細胞での脂肪毒性における小胞体ストレス応答の役割の解明, 第58回日本糖尿病学会年次学術集会, 2015年5月.
55.	三宅雅人, 倉橋清衛, 張君, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : 肥満に伴う脂肪組織での慢性炎症の増悪プロセスへの小胞体ストレス応答経路の関与, 第37回日本分子生物学会年会, 2014年11月.
56.	倉橋清衛, 森智子, 宮本千伸, 津川和江, 親泊美帆, 高原一菜, 佐藤亮祐, 木村千寿子, 三宅雅人, 松本俊夫, 親泊政一 : 飽和脂肪酸は膵β細胞の小胞体膜の組成を変化させ，PERK 経路の活性化による翻訳抑制を介してインスリン分泌を低下させる, 第9回臨床ストレス応答学会大会, 2014年11月.
57.	張君, 三宅雅人, 津川和江, 親泊政一 : CRISPR/Cas9 を用いた小胞体ストレス応答伝達タンパク質の検証, 第9回臨床ストレス応答学会大会, 2014年11月.
58.	谷内秀輔, 三宅雅人, 津川和江, 親泊政一 : Integrated stress response を担う第 5 の eIF2αキナーゼが存在する可能性の CRISPR/Cas9 システムを用いた検証, 第9回臨床ストレス応答学会大会, 2014年11月.
59.	福田寛, 三宅雅人, 平井寛人, 寺西研二, 下村直行, 親泊政一 : ナノ秒パルス電界による HeLa細胞，HEK293細胞の活性化, 平成26年度電気関係学会四国支部連合大会講演論文集, 239, 2014年9月.
60.	野村明利, 三宅雅人, 小倉淳, 森智子, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : 小胞体ストレスなどにより活性化されるeIF2αリン酸化シグナルによる脂肪細胞機能調節, 第8回小胞体ストレス研究会, 2013年10月.
61.	長野明彦, 三宅雅人, 平井寛人, 寺西研二, 下村直行, 親泊政一 : パルス高電界による骨格筋機能制御の基礎研究, 平成25年度電気関係学会四国支部連合大会講演論文集, 240, 2013年9月.
62.	野村明利, 三宅雅人, 小倉淳, 森智子, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : ポスター発表小胞体ストレスなどにより活性化されるeIF2αリン酸化シグナルによる脂肪細胞機能調節の解明, 第86回日本生化学会大会, 2013年9月.
63.	倉橋清衛, 森智子, 野村明利, 小倉淳, 津川和江, 宮本千伸, 三宅雅人, 親泊美帆, 松本俊夫, 親泊政一 : 飽和脂肪酸は小胞体膜の流動性低下によるPERK経路の活性化を介して膵β細胞におけるインスリン分泌を低下させる, 第86回日本生化学会大会, 2013年9月.
64.	野村明利, 三宅雅人, 小倉淳, 森智子, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : 小胞体ストレスなどにより活性化されるeIF2αリン酸化シグナルによる脂肪細胞機能調節の解明, 第86回日本生化学会大会, 2013年9月.
65.	倉橋清衛, 森智子, 野村明利, 小倉淳, 津川和江, 宮本千伸, 三宅雅人, 親泊美帆, 松本俊夫, 親泊政一 : ポスター発表飽和脂肪酸は小胞体膜の流動性低下によるPERK経路の活性化を介して膵β細胞におけるインスリン分泌を低下させる, 第86回日本生化学会大会, 2013年9月.
66.	三宅雅人, 野村明利, 小倉淳, 高原一菜, 佐藤亮祐, 倉橋清衛, 親泊美帆, 井上寛, 親泊政一 : 骨格筋での小胞体ストレスなどからのeIF2αリン酸化はFgf21発現を誘導しエネルギー消費の増加によって食事性肥満を防ぐ, 第86回日本生化学会大会, 2013年9月.
67.	佐藤亮祐, 三宅雅人, 倉橋清衛, 高原一菜, 野村明利, 津川和江, 安井夏生, 親泊政一 : 軟骨異形成症の原因である変異型FGFR3は小胞体ストレスを介して軟骨細胞のアポトーシスを誘導する, 第86回日本生化学会大会, 2013年9月.
68.	高原一菜, 三宅雅人, 野村明利, 小倉淳, 親泊美帆, 森智子, 宮本千伸, 三浦直子, 津川和江, 田中栄二, 森和俊, 親泊政一 : 軟骨異形成症の原因である変異型FGFR3は小胞体ストレスを介して軟骨細胞のアポトーシスを誘導する, 2013年9月.
69.	高原一菜, 三宅雅人, 野村明利, 小倉淳, 親泊美帆, 森智子, 宮本千伸, 三浦直子, 津川和江, 田中栄二, 森和俊, 親泊政一 : 小胞体ストレス応答伝達タンパク質ATF6-alphaとATF6-betaの代謝における役割, 第86回日本生化学会大会, 2013年9月.
70.	野村明利, 三宅雅人, 小倉淳, 森智子, 津川和江 : 小胞体ストレスなどにより活性化されるeIF2αリン酸化シグナルによる脂肪細胞機能調節の解明, 第86回日本生化学会大会, 2013年9月.
71.	野村明利, 三宅雅人, 井上寛, 小倉淳, 森智子, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : 小胞体ストレスなどにより活性化されるPERK-eIF2αリン酸化シグナルによる脂肪細胞機能調節の解明, 第54回日本生化学会中国・四国支部例会, 2013年6月.
72.	三宅雅人, 野村明利, 高原一菜, 小倉淳, 佐藤亮祐, 倉橋清衛, 親泊美帆, 井上寛, 親泊政一 : 骨格筋における小胞体ストレスなどによるeIF2αリン酸化は全身のエネルギー消費を増加させて肥満を抑制する, 第56回日本糖尿病学会年次学術集会, 2013年5月.
73.	倉橋清衛, 三浦直子, 宮本千伸, 津川和江, 森智子, 親泊美帆, 三宅雅人, 小倉淳, 松本俊夫, 親泊政一 : 膵β細胞における飽和脂肪酸による脂肪毒性に小胞体膜流動性の低下とPERK経路が影響する, 第56回日本糖尿病学会年次学術集会, 2013年5月.
74.	野村明利, 三宅雅人, 井上寛, 小倉淳, 森智子, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : 小胞体ストレスなどにより活性化されるPERK-eIF2αリン酸化シグナルによる脂肪細胞機能調節の解明, 第56回日本糖尿病学会年次学術集会, 2013年5月.
75.	三宅雅人, 野村明利, 高原一菜, 佐藤亮祐, 倉橋清衛, 親泊美帆, 井上寛, 親泊政一 : 骨格筋における小胞体ストレスなどからのeIF2αリン酸化はエネルギー消費を制御して食事性肥満を防ぐ, 第85回日本生化学会大会, 2012年12月.
76.	倉橋清衛, 森智子, 井上寛, 小倉淳, 津川和江, 三宅雅人, 井上寛, 松本俊夫, 親泊政一 : 飽和脂肪酸による膵β細胞のインスリン分泌低下には小胞体膜流動性の変化による小胞体ストレスが関与し，PERK経路の活性化により改善される, 第85回日本生化学会大会, 2012年12月.
77.	野村明利, 三宅雅人, 井上寛, 小倉淳, 森智子, 津川和江, 宮本千伸, 親泊美帆, 親泊政一 : 小胞体ストレスなどにより活性化されるPERK-eIF2αリン酸化シグナルによる脂肪細胞機能調節の解明, 第85回日本生化学会大会, 2012年12月.
78.	佐藤亮祐, 三宅雅人, 倉橋清衛, 高原一菜, 野村明利, 津川和江, 小倉淳, 井上寛, 安井夏生, 親泊政一 : FGFR3遺伝子異常による軟骨異形成症における小胞体ストレスの関与, 第85回日本生化学会大会, 2012年12月.
79.	高原一菜, 伊藤太二, 森智子, ロバートゼング, 船橋茉莉, 宮本千伸, 香川聖子, 三宅雅人, 親泊美帆, 津川和江, 田中栄二, 森和俊, 親泊政一 : DSS誘発性大腸炎モデルを用いたATF6αとATF6βの機能解析, 第85回日本生化学会大会, 2012年12月.
80.	三宅雅人, 野村明利, 高原一菜, 佐藤亮祐, 倉橋清衛, 親泊美帆, 井上寛, 親泊政一 : 骨格筋での小胞体ストレスなどによる eIF2a リン酸化はエネルギー消費を増大させて肥満を抑制する, 第 24 回分子糖尿病学シンポジウム, 2012年12月.
81.	三宅雅人, 野村明利, 高原一菜, 佐藤亮祐, 倉橋清衛, 親泊美帆, 井上寛, 親泊政一 : 骨格筋での小胞体ストレスなどによる eIF2αリン酸化はエネルギー消費を増大させて肥満を抑制する, 第7回臨床ストレス応答学会大会, 2012年11月.
82.	三宅雅人, 野村明利, 高原一菜, 小倉淳, 佐藤亮祐, 倉橋清衛, 親泊美帆, 井上寛, 親泊政一 : 骨格筋での小胞体ストレスなどによる eIF2a リン酸化はエネルギー消費を増大させて肥満を抑制する, 第7回小胞体ストレス研究会, 2012年11月.
83.	佐藤亮祐, 三宅雅人, 倉橋清衛, 高原一菜, 野村明利, 津川和江, 小倉淳, 親泊政一 : 小胞体ストレス伝達タンパク質ATF6βは成長軟骨細胞の機能成熟に重要である, 第7回小胞体ストレス研究会, 2012年11月.
84.	高原一菜, 伊藤太二, 森智子, Robert Zeng, 船橋茉莉, 宮本千伸, 香川聖子, 三宅雅人, 親泊美帆, 田中栄二, 森和俊, 親泊政一 : DSS誘発性大腸炎におけるATF6αとATF6βの役割, 第84回日本生化学会大会, 2011年9月.

その他・研究会:

1.	倉橋清衛, 森智子, 宮本千伸, 津川和江, 親泊美帆, 高原一菜, 佐藤亮祐, 木村千寿子, 三宅雅人, 松本俊夫, 親泊政一 : 飽和脂肪酸は膵β細胞の小胞体膜の組成を変化させ，PERK 経路の活性化による翻訳抑制を介してインスリン分泌を低下させる, 第26回分子糖尿病学シンポジウム, 2014年12月.
2.	三宅雅人, 倉橋清衛, 森智子, 宮本千伸, 津川和江, 三浦恭子, 北原吉朗, 親泊美帆, 親泊政一 : 小胞体ストレス応答を制御する新規化合物によるインスリン生合成の促進, 第9回小胞体ストレス研究会, 2014年7月.
3.	張君, 三宅雅人, 親泊政一 : ゲノム編集技術を用いた小胞体ストレス応答の解析, 第9回小胞体ストレス研究会, 2014年7月.
4.	佐藤亮祐, 三宅雅人, 松尾顕, 張君, 谷内秀輔, 倉橋清衛, 高原一菜, 久永哲, 西良浩一, 親泊政一 : 軟骨分化におけるATF6βの役割, 第9回小胞体ストレス研究会, 2014年7月.
5.	倉橋清衛, 森智子, 宮本千伸, 津川和江, 親泊美帆, 高原一菜, 佐藤亮祐, 木村千寿子, 三宅雅人, 松本俊夫, 親泊政一 : 飽和脂肪酸による膵β細胞の小胞体膜の組成変化は，PERK経路活性化を遷延させ翻訳抑制を介してインスリン分泌を低下させる, 第9回小胞体ストレス研究会, 2014年7月.
6.	谷内秀輔, 三宅雅人, 親泊政一 : ゲノム編集技術を用いたIntegrated Stress Response(ISR)の解析, 第9回小胞体ストレス研究会, 2014年7月.
7.	三宅雅人, 野村明利, 小倉淳, 高原一菜, 佐藤亮祐, 倉橋清衛, 親泊美帆, 井上寛, 親泊政一 : 骨格筋における小胞体ストレスなどによるeIF2αリン酸化はFgf21を介したエネルギー消費の増加によって食事性肥満を防ぐ, 第31回内分泌代謝学サマーセミナー, 2013年7月.

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

小胞体ストレス応答転写因子ATF6βによる肥満・糖尿病の増悪化機構の解明 (研究課題/領域番号: 20K08909 )
脂肪細胞での統合的ストレス応答経路による肥満制御機構の解明 (研究課題/領域番号: 17K09862 )
統合的ストレス応答を標的としたサルコペニア治療薬の探索 (研究課題/領域番号: 16H05222 )
加齢に伴う骨格筋萎縮における小胞体ストレス応答の機能解明 (研究課題/領域番号: 26350893 )
小胞体ストレス応答因子ATF6βによる生体機能制御とその破綻による疾患発症の解明 (研究課題/領域番号: 25293080 )
運動で誘導される小胞体からのｅＩＦ２αリン酸化の骨格筋機能制御における役割 (研究課題/領域番号: 24700698 )
筋形成抑制因子マイオスタチンの機能制御における栄養センサーAMPKの作用 (研究課題/領域番号: 22880006 )
小胞体ストレス応答シグナルによる糖・脂質代謝制御機構の解明とその臨床応用 (研究課題/領域番号: 22390061 )
研究者番号（30588976）による検索

准教授 : 三宅雅人

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科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

准教授 : 三宅 雅人

研究活動

専門分野

研究テーマ

著書・論文

学術論文(審査論文):

総説・解説:

国際会議:

国内講演発表:

その他・研究会:

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

准教授 : 三宅雅人