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Regulating mechanisms of podocyte differentiation by vitamin D receptor signaling

Research Project

Project/Area Number 22K08321
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionOkinaka Memorial Institute for Medical Research (2023-2024)
Tokai University (2022)

Principal Investigator

Wada Takehiko  (財)冲中記念成人病研究所, その他部局等, 研究員 (90447409)

Co-Investigator(Kenkyū-buntansha) 深川 雅史  東海大学, 医学部, 客員教授 (00211516)
豊田 雅夫  東海大学, 医学部, 准教授 (00349383)
Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsポドサイト / 糖尿病 / ビタミンD / 細胞分化 / 細胞周期調節蛋白 / 細胞周期 / 糖尿病性腎症 / 分化調節
Outline of Research at the Start

腎臓の濾過装置を構成するポドサイトは、高度に分化して尿に蛋白が漏出することを防止する重要な細胞です。当研究グループでは、糖尿病による腎障害の原因としてポドサイトの障害のメカニズムに注目し、それに対する防御機構について研究しています。この研究ではビタミンDの作用による細胞内シグナル伝達がポドサイトの分化状態を維持することが障害に対する防御機構となるという仮説を立て、それを検証する予定です。

Outline of Final Research Achievements

In this study, we found that stimuli associated with diabetes are linked to renal damage through changes in podocytes (glomerular epithelial cells), which play an main role in the renal filtration barrier, and that active vitamin D protects these cells by regulating cell cycle regulatory protein p21. Notably, it was also observed that active vitamin D itself increases vitamin D receptors in these cells, suggesting the possibility of a positive feedback mechanism that amplifies its protective effects.

Academic Significance and Societal Importance of the Research Achievements

ポドサイト(糸球体足細胞)は腎臓において濾過バリア機能の中心的役割を果たしていますが、その障害は蛋白尿などの尿所見異常のみならず、腎臓全体の機能障害に直結することが知られています。本研究ではビタミンDがポドサイトの分化段階の変化を抑制することにより、糖尿病などに起因するポドサイト障害の防止に働く可能性を見出すことができました。本研究成果が将来的に蛋白尿を有する腎障害の治療法開発の一助になることが期待されます。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (40 results)

All 2025 2024 2023 2022 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 11 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (9 results) Remarks (2 results)

  • [Journal Article] Fibroblast Growth Factor 23, Endogenous Erythropoietin, Erythropoiesis-Stimulating Agents, and Erythropoietin Resistance in Hemodialysis Patients2025

    • Author(s)
      Hamano Naoto、Komaba Hirotaka、Tanaka Hisae、Takahashi Hiroo、Takahashi Yuichiro、Hyodo Toru、Hida Miho、Suga Takao、Wada Takehiko、Kakuta Takatoshi、Fukagawa Masafumi
    • Journal Title

      American Journal of Nephrology

      Volume: ー Issue: 4 Pages: 403-411

    • DOI

      10.1159/000543506

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human immunodeficiency virus-associated nephropathy mainly due to cellular variant of focal segmental glomerulosclerosis2025

    • Author(s)
      Tanimizu Hikaru、Sawa Naoki、Sekine Akinari、Oba Yuki、Yamanouchi Masayuki、Hasegawa Eiko、Suwabe Tatsuya、Hoshino Junichi、Kinowaki Keiichi、Kono Kei、Ohashi Kenichi、Kanetsuna Yukiko、Honda Kazuho、Joh Kensuke、Yamaguchi Yutaka、Wada Takehiko、Ubara Yoshifumi
    • Journal Title

      CEN Case Reports

      Volume: - Issue: 3 Pages: 345-350

    • DOI

      10.1007/s13730-025-00979-2

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glomerular Microangiopathy-like Nephropathy Caused by Hyperthyroidism2024

    • Author(s)
      Katayama Yuri、Sawa Naoki、Kurihara Shigekazu、Ikuma Daisuke、Oba Yuki、Sekine Akinari、Yamanouchi Masayuki、Hasegawa Eiko、Suwabe Tatsuya、Wada Takehiko、Kono Kei、Kinowaki Keiichi、Ohashi Kenichi、Tsuchiya Yoshiki、Ubara Yoshifumi
    • Journal Title

      Internal Medicine

      Volume: 63 Issue: 12 Pages: 1765-1770

    • DOI

      10.2169/internalmedicine.2436-23

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2024-06-15
    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Syphilis-related Membranous Nephropathy in a 35-year-old Woman2024

    • Author(s)
      Nakayama Yuki、Yamanouchi Masayuki、Mizuno Hiroki、Suwabe Tatsuya、Sekine Akinari、Ikuma Daisuke、Hasegawa Eiko、Oba Yuki、Kono Kei、Kinowaki Keiichi、Ohashi Kenichi、Wada Takehiko、Sawa Naoki、Ubara Yoshifumi
    • Journal Title

      Internal Medicine

      Volume: 63 Issue: 10 Pages: 1429-1432

    • DOI

      10.2169/internalmedicine.2380-23

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2024-05-15
    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lupus nephritis and related renal disease: review from case series2024

    • Author(s)
      Ubara Yoshifumi、Sawa Naoki、Wada Takehiko、Kono Kei、Ohashi Kenichi
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 29 Issue: 5 Pages: 507-520

    • DOI

      10.1007/s10157-024-02603-6

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dapagliflozin treatment in patients with chronic kidney disease associated with autosomal dominant polycystic kidney disease2024

    • Author(s)
      Yoshimoto Masatoshi、Sekine Akinari、Suwabe Tatsuya、Oba Yuki、Mizuno Hiroki、Yamanouchi Masayuki、Ubara Yoshifumi、Hoshino Junichi、Inoue Noriko、Tanaka Kiho、Hasegawa Eiko、Sawa Naoki、Wada Takehiko
    • Journal Title

      Clinical Kidney Journal

      Volume: 17 Issue: 8

    • DOI

      10.1093/ckj/sfae186

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of serum sodium levels with fractures and mortality in patients undergoing maintenance hemodialysis2024

    • Author(s)
      Soeda Keisuke、Komaba Hirotaka、Nakagawa Yosuke、Kawabata Chiaki、Wada Takehiko、Takahashi Hiroo、Takahashi Yuichiro、Hyodo Toru、Hida Miho、Suga Takao、Kakuta Takatoshi、Fukagawa Masafumi
    • Journal Title

      Journal of Nephrology

      Volume: - Issue: 5 Pages: 1339-1349

    • DOI

      10.1007/s40620-024-01904-z

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preference for anti-phospholipase A2 receptor antibody assay in patients with suspected membranous nephropathy: a survey study on medical practice after publication of Japanese Guidelines for Nephrotic Syndrome 20202024

    • Author(s)
      Sasaki Sho、Shimizu Sayaka、Nakaya Izaya、Miyaoka Yoshitaka、Koizumi Masahiro、Nishiwaki Hiroki、Sofue Tadashi、Ishimoto Takuji、Kurita Noriaki、Wada Takehiko
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 28 Issue: 6 Pages: 531-538

    • DOI

      10.1007/s10157-024-02462-1

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] De novo posttransplant membranous nephropathy after COVID-19 vaccination 9?years after renal transplantation in a patient with polycystic kidney disease2024

    • Author(s)
      Fukuda Miruzato、Yokoyama Takayoshi、Miki Katsuyuki、Yamanouchi Masayuki、Ikuma Daisuke、Mizuno Hiroki、Oba Yuki、Inoue Noriko、Sekine Akinari、Tanaka Kiho、Hasegawa Eiko、Suwabe Tatsuya、Wada Takehiko、Kono Kei、Kinowaki Keiichi、Ohashi Kenichi、Yamaguchi Yutaka、Nakamura Yuki、Ishii Yasuo、Sawa Naoki、Ubara Yoshifumi
    • Journal Title

      CEN Case Reports

      Volume: - Issue: 6 Pages: 434-439

    • DOI

      10.1007/s13730-024-00864-4

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Japanese clinical practice patterns of rituximab treatment for minimal change disease in adults 2021: A web-based questionnaire survey of certified nephrologists2024

    • Author(s)
      Koizumi Masahiro、Ishimoto Takuji、Shimizu Sayaka、Sasaki Sho、Kurita Noriaki、Wada Takehiko
    • Journal Title

      PLOS ONE

      Volume: 19 Issue: 3 Pages: e0299053-e0299053

    • DOI

      10.1371/journal.pone.0299053

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Japanese clinical practice patterns of primary nephrotic syndrome 2021: a web-based questionnaire survey of certified nephrologists2023

    • Author(s)
      Wada Takehiko、Shimizu Sayaka、Koizumi Masahiro、Sofue Tadashi、Nishiwaki Hiroki、Sasaki Sho、Nakaya Izaya、Oe Yuji、Ishimoto Takuji、Furuichi Kengo、Okada Hirokazu、Kurita Noriaki
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 27 Issue: 9 Pages: 767-775

    • DOI

      10.1007/s10157-023-02366-6

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Practice patterns of rituximab for primary membranous nephropathy 2021 in Japan: a web-based survey of board-certified nephrologists2023

    • Author(s)
      Miyaoka Yoshitaka、Kurita Noriaki、Sofue Tadashi、Nishiwaki Hiroki、Koizumi Masahiro、Shimizu Sayaka、Sasaki Sho、Ishimoto Takuji、Wada Takehiko
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 28 Issue: 3 Pages: 217-224

    • DOI

      10.1007/s10157-023-02425-y

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Demographics and treatment of patients with primary nephrotic syndrome in Japan using a national registry of clinical personal records2023

    • Author(s)
      Nakagawa Naoki、Kimura Tomonori、Sakate Ryuichi、Wada Takehiko、Furuichi Kengo、Okada Hirokazu、Isaka Yoshitaka、Narita Ichiei
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1

    • DOI

      10.1038/s41598-023-41909-5

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients2023

    • Author(s)
      Ohashi Yuki、Toyoda Masao、Saito Nobumichi、Koizumi Masahiro、Kanai Genta、Komaba Hirotaka、Kimura Moritsugu、Wada Takehiko、Takahashi Hiroo、Takahashi Yuichiro、Ishida Naoto、Kakuta Takatoshi、Fukagawa Masafumi、Ichida Kimiyoshi
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 93-93

    • DOI

      10.1038/s41598-022-26519-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced podocyte differentiation and changing drug toxicity sensitivity through pressure-controlled mechanical filtration stress on a glomerulus-on-a-chip2023

    • Author(s)
      Doi Kotaro、Kimura Hiroshi、Kim Soo Hyeon、Kaneda Shohei、Wada Takehiko、Tanaka Tetsuhiro、Shimizu Akira、Sano Takanori、Chikamori Masamichi、Shinohara Marie、Matsunaga Yukiko T.、Nangaku Masaomi、Fujii Teruo
    • Journal Title

      Lab on a Chip

      Volume: 23 Issue: 3 Pages: 437-450

    • DOI

      10.1039/d2lc00941b

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum Sclerostin Levels and Mortality in Hemodialysis Patients: An 8-Year Prospective Study2022

    • Author(s)
      Nakagawa Yosuke、Komaba Hirotaka、Wada Takehiko、Takahashi Hiroo、Takahashi Yuichiro、Hyodo Toru、Hida Miho、Suga Takao、Kakuta Takatoshi、Fukagawa Masafumi
    • Journal Title

      American Journal of Nephrology

      Volume: 53 Issue: 11-12 Pages: 767-774

    • DOI

      10.1159/000528795

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hyporesponsiveness to erythropoiesis-stimulating agent in non-dialysis-dependent CKD patients: The BRIGHTEN study2022

    • Author(s)
      Narita Ichiei、Wada Takehiko、Tsubakihara Yoshiharu, et al.
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 11 Pages: e0277921-e0277921

    • DOI

      10.1371/journal.pone.0277921

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential progression biomarkers of diabetic kidney disease determined using comprehensive machine learning analysis of non-targeted metabolomics2022

    • Author(s)
      Hirakawa Yosuke、Yoshioka Kentaro、Kojima Kensuke、Yamashita Yasuho、Shibahara Takuma、Wada Takehiko、Nangaku Masaomi、Inagi Reiko
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 16287-16287

    • DOI

      10.1038/s41598-022-20638-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Protective role of active vitamin D in TGF-β1-associated podocyte injury through inhibition of p21 upregulation.2024

    • Author(s)
      Takehiko Wada, Kaichiro Sawada, Hirotaka Komaba, Masafumi Fukagawa
    • Organizer
      ASN KIDNEY WEEK 2024
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Practical kidney function assessment in elderly patients receiving cisplatin2024

    • Author(s)
      Akinari Sekine, Noriko Inoue, Kiho Tanaka, Eiko Hasegawa, Takehiko Wada
    • Organizer
      Kidney Health In Aging and Aged Societies JSN/ERA symposium
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Onconephrologyとendocrine oncologyにみる分野横断的医療2024

    • Author(s)
      和田健彦
    • Organizer
      第46会日本内分泌学会東北地方会・第34回東北内分泌研究会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] 微小変化型ネフローゼ症候群に対するリツキシマブ療法2023

    • Author(s)
      和田健彦
    • Organizer
      第66回日本腎臓学会学術総会
    • Related Report
      2023 Research-status Report
  • [Presentation] 胸腺腫を背景に発症したステロイド抵抗性微小変化型ネフローゼ症候群の一例2023

    • Author(s)
      小澤征良,関根章成,井上典子,田中希穂,長谷川詠子,乳原善文,澤直樹,和田健彦
    • Organizer
      第53回日本腎臓学会東部学術大会
    • Related Report
      2023 Research-status Report
  • [Presentation] 巣状分節性糸球体硬化症診療・国際間比較と今後2022

    • Author(s)
      和田健彦
    • Organizer
      第65回日本腎臓学会学術総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 一般人口と比較した透析患者のがん死亡リスク2022

    • Author(s)
      和田 健彦、駒場 大峰、深川 雅史
    • Organizer
      第67回日本透析医学会学術集会・総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 一次性ネフローゼ症候群の診療実態-腎臓専門医アンケート調査-2022

    • Author(s)
      和田 健彦、栗田 宜明、清水 さやか、佐々木 彰、石本 卓嗣、古市 賢吾、岡田 浩一.
    • Organizer
      第65回日本腎臓学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 成人微小変化型ネフローゼ症候群におけるリツキシマブの使用実態-腎臓専門医アンケート調査-2022

    • Author(s)
      石本卓嗣, 栗田宜明, 清水さやか, 佐々木彰, 小泉賢洋, 和田健彦
    • Organizer
      第65回日本腎臓学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 抗PLA2R抗体の測定実態と関連因子-腎臓専門医アンケート調査-2022

    • Author(s)
      佐々木彰, 中屋来哉, 石本卓嗣, 清水さやか, 栗田宜明, 和田健彦
    • Organizer
      第65回日本腎臓学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 膜性腎症におけるリツキシマブの使用実態と差し控えの理由-腎臓専門医アンケート調査-2022

    • Author(s)
      宮岡良卓, 栗田宜明, 清水さやか, 祖父江理, 石本卓嗣, 佐々木彰, 和田健彦
    • Organizer
      第65回日本腎臓学会学術総会
    • Related Report
      2022 Research-status Report
  • [Book] 今日の治療指針2025年版2025

    • Author(s)
      和田健彦(福井次矢・髙木誠・小室一成総編集)
    • Total Pages
      2208
    • Publisher
      医学書院
    • ISBN
      9784260057172
    • Related Report
      2024 Annual Research Report
  • [Book] 今日の診断指針第9版2025

    • Author(s)
      和田健彦(永井良三総編集)
    • Total Pages
      2016
    • Publisher
      医学書院
    • ISBN
      9784260054805
    • Related Report
      2024 Annual Research Report
  • [Book] 臨床検査ガイド2024

    • Author(s)
      和田健彦(大西宏明編集)
    • Total Pages
      1136
    • Publisher
      文光堂
    • ISBN
      9784830680380
    • Related Report
      2024 Annual Research Report
  • [Book] 専門医のための腎臓病学2023

    • Author(s)
      和田 健彦
    • Total Pages
      680
    • Publisher
      医学書院
    • ISBN
      9784260051002
    • Related Report
      2023 Research-status Report
  • [Book] 最新ガイドラインに基づく 腎・透析 診療指針 2023-’242023

    • Author(s)
      岡田浩一(編)
    • Total Pages
      316
    • Publisher
      総合医学社
    • ISBN
      9784883789399
    • Related Report
      2023 Research-status Report
  • [Book] 腎臓内科診療の掟2023

    • Author(s)
      髙野秀樹・南学正臣(編)
    • Total Pages
      374
    • Publisher
      中外医学社
    • ISBN
      9784498224902
    • Related Report
      2023 Research-status Report
  • [Book] わかりやすい内科学2023

    • Author(s)
      井村裕夫ら
    • Total Pages
      1016
    • Publisher
      文光堂
    • ISBN
      9784830620676
    • Related Report
      2023 Research-status Report
  • [Book] よくわかる老年腫瘍学2023

    • Author(s)
      日本がんサポーティブケア学会
    • Total Pages
      336
    • Publisher
      金原出版
    • ISBN
      9784307102209
    • Related Report
      2023 Research-status Report
  • [Book] ケースで学ぶ 実践!水・電解質診療2022

    • Author(s)
      和田健彦
    • Total Pages
      248
    • Publisher
      文光堂
    • ISBN
      9784830620652
    • Related Report
      2022 Research-status Report
  • [Remarks] 冲中記念成人病研究所ホームページ

    • URL

      https://okiken.tokyo

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
  • [Remarks] 東海大学医学部腎内分泌代謝内科ホームページ

    • URL

      http://u-tokai-nem.jp

    • Related Report
      2024 Annual Research Report 2023 Research-status Report 2022 Research-status Report

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Published: 2022-04-19   Modified: 2026-01-16  

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