Tokushima University / Educator and Researcher Directory --- Nagai, Takashi

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Tokushima University ⟩ University Hospital ⟩ Clinical Division ⟩ Department of Pediatrics,Obstetrics and Gynecology ⟩ Pediatrics ⟩

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Research

Field of Study

Subject of Study

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Academic Paper (Judged Full Paper):

1.	Tomoki Hattori, Keisuke Fujioka, Takashi Nagai, Shuji Kondo, Shoji Kagami, Masahiro Hirayama and Maki Urushihara : Intrarenal renin-angiotensin system activation and macrophage infiltrations in pediatric chronic glomerulonephritis., Pediatric Nephrology, 2023. (Summary) The data indicates that UAGT and UMCP-1 are useful biomarkers of the degree of glomerular injury during RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis. (Tokushima University Institutional Repository) ● Metadata: 118974 (Link to Publication Site) ● Publication site (DOI): 10.1007/s00467-023-06026-5 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37231123 ● Search Scopus @ Elsevier (PMID): 37231123 ● Search Scopus @ Elsevier (DOI): 10.1007/s00467-023-06026-5 (Tokushima University Institutional Repository: 118974, DOI: 10.1007/s00467-023-06026-5, PubMed: 37231123)
2.	Yuki Sakaki, Maki Urushihara, Takashi Nagai, Keisuke Fujioka, Shuji Kondo, Yukiko Kinoshita, Tomoki Hattori and Shoji Kagami : Urinary angiotensin converting enzyme 2 and disease activity in pediatric IgA nephropathy, The Journal of Medical Investigation : JMI, Vol.68, No.3.4, 292-296, 2021. (Summary) Background : Our previous studies demonstrated that the intrarenal renin-angiotensin system (RAS) status was activated in pediatric patients with chronic glomerulonephritis. In the present study, we tested the hypothesis that angiotensin-converting enzyme 2 (ACE2) expression in the kidney is associated with the development of pediatric IgA nephropathy. Methods : We analyzed urinary ACE2 levels and ACE2 expression in the kidney tissues of pediatric patients with IgA nephropathy treated with RAS blockade. Paired tests were used to analyze changes from the first to the second biopsy. Results : Urinary ACE2 levels were significantly decreased after RAS blockade treatment, accompanied by decreased ACE2 expression levels in kidney tissues, urinary protein levels and mesangial hypercellularity scores. Urinary ACE2 levels at the first biopsy were positively correlated with the ACE2 expression levels. Conclusions : These data suggest that urinary ACE2 is associated with ACE2 expression in the diseased kidney, which correlates with the pathogenesis of IgA nephropathy in pediatric patients. J. Med. Invest. 68 : 292-296, August, 2021. (Keyword) Angiotensin-Converting Enzyme 2 / Biopsy / Child / Glomerulonephritis, IGA / Humans / Kidney / Renin-Angiotensin System (Tokushima University Institutional Repository) ● Metadata: 116498 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.68.292 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34759147 ● Summary page in Scopus @ Elsevier: 2-s2.0-85119281201 (Tokushima University Institutional Repository: 116498, DOI: 10.2152/jmi.68.292, PubMed: 34759147, Elsevier: Scopus)
3.	Maki Urushihara, Shuji Kondo, Yukiko Kinoshita, Natsuko Ozaki, Ariunbold Jamba, Takashi Nagai, Keisuke Fujioka, Tomoki Hattori and Shoji Kagami : (Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis., American Journal of Physiology, Renal Physiology, Vol.319, No.4, F571-F578, 2020. (Summary) (Pro)renin receptor [(P)RR] has multiple functions, but its regulation and role in the pathogenesis in glomerulonephritis (GN) are poorly defined. The aims of the present study were to determine the effects of direct renin inhibition (DRI) and demonstrate the role of (P)RR on the progression of crescentic GN. The anti-glomerular basement membrane nephritis rat model developed progressive proteinuria (83.64 ± 10.49 mg/day) and glomerular crescent formation (percent glomerular crescent: 62.1 ± 2.3%) accompanied by increased macrophage infiltration and glomerular expression of monocyte chemoattractant protein (MCP)-1, (P)RR, phospho-extracellular signal-regulated kinase (ERK)1/2, Wnt4, and active β-catenin. Treatment with DRI ameliorated proteinuria (20.33 ± 5.88 mg/day) and markedly reduced glomerular crescent formation (20.9 ± 2.6%), induction of macrophage infiltration, (P)RR, phospho-ERK1/2, Wnt4, and active β-catenin. Furthermore, primary cultured parietal epithelial cells stimulated by recombinant prorenin showed significant increases in cell proliferation. Notably, while the ERK1/2 inhibitor PD98059 or (P)RR-specific siRNA treatment abolished the elevation in cell proliferation, DRI treatment did not abrogate this elevation. Moreover, cultured mesangial cells showed an increase in prorenin-induced MCP-1 expression. Interestingly, (P)RR or Wnt4-specific siRNA treatment or the β-catenin antagonist XAV939 inhibited the elevation of MCP-1 expression, whereas DRI did not. These results suggest that (P)RR regulates glomerular crescent formation via the ERK1/2 signaling and Wnt/β-catenin pathways during the course of anti-glomerular basement membrane nephritis and that DRI mitigates the progression of crescentic GN through the reduction of (P)RR expression but not inhibition of prorenin binding to (P)RR. (Keyword) Amides / Animals / Cell Proliferation / Cells, Cultured / Disease Models, Animal / Fumarates / Glomerulonephritis / male / Mesangial Cells / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / phosphorylation / Rats, Inbred WKY / Receptors, Cell Surface / Wnt Signaling Pathway / Wnt4 Protein / beta Catenin (Link to Publication Site) ● Publication site (DOI): 10.1152/ajprenal.00250.2020 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32830537 ● Summary page in Scopus @ Elsevier: 2-s2.0-85091470044 (DOI: 10.1152/ajprenal.00250.2020, PubMed: 32830537, Elsevier: Scopus)
4.	Keisuke Fujioka, Takashi Nagai, Yukiko Kinoshita, Maki Urushihara, Yuko Hamasaki, Seiichiro Shishido and Shoji Kagami : Successful treatment with voriconazole combined with amphotericin B-liposome for fluconazole-resistant pulmonary cryptococcosis after renal transplantation., CEN Case Reports, Vol.8, No.4, 261-265, 2019. (Summary) Cryptococcosis is an invasive fungal infection that is common among organ transplant recipients, and it is challenging to treat among these patients because of their immunocompromised status. Fluconazole (FLCZ) is recommended as a first-line treatment modality for pulmonary cryptococcosis in organ transplant recipients. However, cases of FLCZ resistance among Cryptococcus neoformans isolates have been reported from the Asia Pacific region. Previous studies have reported the efficacy of voriconazole (VRCZ) in patients with FLCZ-resistant fungal infections. Herein, we report a case of FLCZ-resistant pulmonary cryptococcosis after renal transplantation that was successfully treated with VRCZ combined with amphotericin B-liposome (L-AMB). The patient was a-23-year-old woman who underwent living-donor kidney transplantation at age 20 years. She has attended our hospital since before for mental retardation, epilepsy, and dilated cardiomyopathy. At age 23 years, she presented to our hospital with fever and cough. She was diagnosed with pulmonary cryptococcosis based on positive-serum cryptococcal antigen. Chest radiography showed bilateral consolidations. Fosfluconazole (F-FLCZ) was administered, and her condition improved. However, she developed cough and fever again on day 60 of hospitalization. Cryptococcosis recurrence was suspected due to the high degree of cryptococcal antigen titers showed (1:2048) taken on the same day. Therefore, L-AMB was added, and F-FLCZ was substituted with VRCZ. Her condition improved, but L-AMB was discontinued due to hyponatremia, hypokalemia, and elevated serum creatinine. This indicates that VRCZ caused the remission. She was discharged after 6 months of admission. In conclusion, this case shows the efficacy of VRCZ combined with L-AMB for refractory pulmonary cryptococcosis. (Keyword) Amphotericin B / Antifungal Agents / Antigens, Fungal / Combined Modality Therapy / Cryptococcosis / Cryptococcus neoformans / Drug Resistance, Fungal / female / Fluconazole / Humans / Kidney Transplantation / Lung Diseases, Fungal / Radiography, Thoracic / Treatment Outcome / Voriconazole / Young Adult (Link to Publication Site) ● Publication site (DOI): 10.1007/s13730-019-00403-6 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31161376 ● Summary page in Scopus @ Elsevier: 2-s2.0-85085231082 (DOI: 10.1007/s13730-019-00403-6, PubMed: 31161376, Elsevier: Scopus)
5.	Shuji Kondo, Sato Matsuura, Jamba Ariunbold, Yukiko Kinoshita, Maki Urushihara, Kenichi Suga, Natsuko Ozaki, Takashi Nagai, Keisuke Fujioka and Shoji Kagami : Expression of NADPH oxidase and production of reactive oxygen species contribute to ureteric bud branching and nephrogenesis., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 93-98, 2019. (Summary) Ureteric bud branching and nephrogenesis are performed through large-scale proliferation and apoptosis events during renal development. Reactive oxygen species (ROS), produced by NADPH oxidase, may contribute to cell behaviors, including proliferation and apoptosis. We investigated the role of NADPH oxidase expression and ROS production in developing kidneys. Immunohistochemistry revealed that NADPH oxidase componentswere expressed on epithelial cells in ureteric bud branches, as well as on immature glomerular cells and epithelial cells in nephrogenic zones. ROS production, detected by dihydroethidium assay, was strongly observed in ureteric bud branches and nephrogenic zones, corresponding with NADPH oxidase localization. Organ culture of E14 kidneys revealed that the inhibition of NADPH oxidase significantly reduced the number of ureteric bud branches and tips, consistent with reduced ROS production. This was associated with reduced expression of phosphorylated ERK1/2 and increased expression of cleaved caspase-3. Organ culture of E18 kidneys showed that the inhibition of NADPH oxidase reduced nephrogenic zone size, accompanied by reduced ROS production, fewer proliferating cell nuclear antigen-positive cells, lower p-ERK1/2 expression, and increased expression of cleaved caspase-3. These results demonstrate that ROS produced by NADPH oxidase might play an important role in ureteric bud branching and nephrogenesis by regulating proliferation and apoptosis. J.Med. Invest. 66 :93-98, February, 2019. (Keyword) Animals / Caspase 3 / female / Kidney / NADPH Oxidases / Pregnancy / Rats / Rats, Sprague-Dawley / reactive oxygen species / Ureter (Tokushima University Institutional Repository) ● Metadata: 113341 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.66.93 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31064963 ● Summary page in Scopus @ Elsevier: 2-s2.0-85065765015 (Tokushima University Institutional Repository: 113341, DOI: 10.2152/jmi.66.93, PubMed: 31064963, Elsevier: Scopus)
6.	Takashi Nagai, Maki Urushihara, Keisuke Fujioka, Yukiko Kinoshita and Shoji Kagami : 徳島県における小児末期腎不全患者の現況, 日本小児PD・HD研究会雑誌, Vol.29, 6-8, 2017.

Review, Commentary:

1.	Takashi Nagai and Shoji Kagami : IgA腎症・紫斑病性腎炎の治療戦略, Pediatrics of Japan, Vol.59, No.10, 1433-1438, 2018.

Proceeding of Domestic Conference:

1.	Tomoki Hattori, Keisuke Fujioka, Takashi Nagai and Maki Urushihara : 小児慢性糸球体腎炎における腎内レニン・アンジオテンシン系活性化とマクロファージの役割の検討, 第65回日本腎臓学会学術集会, Jun. 2022.
2.	Takashi Nagai, Tomoki Hattori, Keisuke Fujioka and Maki Urushihara : 半月体形成性腎炎に対するERK経路阻害剤の腎炎進展抑制効果, 第65回日本腎臓学会学術集会, Jun. 2022.
3.	Tomoki Hattori, Keisuke Fujioka, Takashi Nagai and Maki Urushihara : 小児慢性糸球体腎炎における腎内レニン・アンジオテンシン系活性化とマクロファージの役割の検討, 第57回日本小児腎臓病学会, May 2022.
4.	Takashi Nagai, 服部共樹, Keisuke Fujioka and Maki Urushihara : ERK経路阻害剤による半月体形成性腎炎抑制効果の検討, 第57回日本小児腎臓病学会, May 2022.
5.	Keisuke Fujioka, Takashi Nagai, 木下ゆき子, Maki Urushihara, 近藤秀治 and Shoji Kagami : 肉眼的血尿を契機に急性尿細管壊死による腎障害を呈したIgA腎症の一例, 第41回日本小児腎不全学会学術集会, Nov. 2019.
6.	Maki Urushihara, Keisuke Fujioka, Takashi Nagai, 近藤秀治 and Shoji Kagami : 小児IgA腎症における腎内レニン・アンジオテンシン系活性化と炎症機序との関係, 第26回日本小児高血圧研究会, Sep. 2019.
7.	Takashi Nagai, Keisuke Fujioka, Maki Urushihara, 近藤秀治 and Shoji Kagami : 急速進行性腎炎症候群を呈した免疫複合体型腎炎の14歳女児例, 第52回日本小児腎臓病学会学術集会, Jun. 2019.
8.	Keisuke Fujioka, Takashi Nagai, 木下ゆき子, Maki Urushihara and Shoji Kagami : 溶連菌感染後急性糸球体腎炎との鑑別を要したC3腎症の1例, 第52回日本小児腎臓病学会学術集会, Jun. 2019.
9.	Keisuke Fujioka, Takashi Nagai, Yukiko Kinoshita, Maki Urushihara and Shoji Kagami : 生体腎移植後に肺クリプトコッカス症を発症し治療に難渋した1例, 第122回日本小児科学会学術集会, Apr. 2019.
10.	Keisuke Fujioka, Takashi Nagai, Maki Urushihara and Shoji Kagami : Silent lupus nephritisの所見を呈した混合性結合組織病の1例, 第70回中国四国小児科学会, Nov. 2018.
11.	Keisuke Fujioka, Takashi Nagai, Maki Urushihara and Shoji Kagami : Silent lupus nephritisの所見を呈した混合性結合組織病の1例, 第35回中国四国小児腎臓病学会, Nov. 2018.
12.	Takashi Nagai, Keisuke Fujioka, Maki Urushihara, Yukiko Kinoshita, Kazuhiro Mori and Shoji Kagami : 腎瘻造設術および片腎摘除術を要したActinotignum schaalii膿腎症の4歳男児例, 第48回日本腎臓学会西部学術集会, Sep. 2018.
13.	Keisuke Fujioka, Takashi Nagai, Yukiko Kinoshita, Maki Urushihara and Shoji Kagami : 生体腎移植後に肺クリプトコッカス症を発症し治療に難渋した1例, 第48回日本腎臓学会西部学術大会, Sep. 2018.
14.	Takashi Nagai, Maki Urushihara, Keisuke Fujioka, Yukiko Kinoshita and Shoji Kagami : 単一県における透析および腎移植症例を通じて考察した小児末期腎不全の地域医療, 第39回日本小児腎不全学会学術集会, Sep. 2017.
15.	Yukiko Kinoshita, Keisuke Fujioka, Takashi Nagai, 尾崎夏子, Maki Urushihara, Shuji Kondo, Hiroyasu Tsukaguchi and Shoji Kagami : ADCK4の遺伝子異常が同定されたステロイド抵抗性ネフローゼ症候群(SRNS)の一男児例, 第52回日本小児腎臓病学会学術集会, Jun. 2017.
16.	Maki Urushihara, Yukiko Kinoshita, Shuji Kondo, Takashi Nagai, Keisuke Fujioka and Shoji Kagami : ラット半月体形成性腎炎モデルにおける(プロ)レニン受容体を介した病態機序と直接レニン阻害薬の治療効果, 第60回日本腎臓学会学術総会, May 2017.
17.	Yukiko Kinoshita, Keisuke Fujioka, Takashi Nagai, 尾崎夏子, Maki Urushihara, Shuji Kondo, 塚口裕康 and Shoji Kagami : ADCK4の遺伝子異常が同定されたステロイド抵抗性ネフローゼ症候群(SRNS)の一例, 第120回日本小児科学会学術集会, Apr. 2017.

Et cetera, Workshop:

1.	Takashi Nagai, Keisuke Fujioka, Maki Urushihara, Shoji Kagami, 山崎博輝, Yukiko Kinoshita and Kazuhiro Mori : 嚥下障害を伴った若年性皮膚筋炎の1例, 第151会日本小児科学会徳島地方会, Dec. 2018.
2.	Keisuke Fujioka, Takashi Nagai, Yukiko Kinoshita, Maki Urushihara and Shoji Kagami : 生体腎移植後に肺クリプトコッカス症を発症し治療に難渋した1例, 第150回日本小児科学会徳島地方会, Jun. 2018.

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

スリット膜機能維持におけるNeurexin-シナプス小胞関連分子相互作用の役割 (Project/Area Number: 24K11405 )
ACE2阻害薬およびERK経路阻害薬による慢性腎炎進展抑制効果の検証 (Project/Area Number: 23K14982 )
The role of ERK pathway inhivitors in rat crescentic glomerulonephritis (Project/Area Number: 19K17302 )
Search by Researcher Number (20835582)