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Role of endothelial dysfunction in diabetic kidney disease

Research Project

Project/Area Number 19K08714
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionFukuoka University

Principal Investigator

Kawanami Daiji  福岡大学, 医学部, 教授 (50568889)

Co-Investigator(Kenkyū-buntansha) 的場 圭一郎  東京慈恵会医科大学, 医学部, 講師 (20459647)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords糖尿病性腎臓病 / 糖尿病性腎症 / Rho-kinase / 血管内皮機能 / 脂肪細胞 / 血管内皮機能障害
Outline of Research at the Start

糖尿病性腎臓病は我が国における透析導入原疾患第一位であり、その原因究明と新たな治療戦略の構築が急務の課題となっている。本研究では、血管内皮機能を調節する因子を欠損させた細胞やマウスを用いて糖尿病モデルを作製し、糖尿病性腎臓病の発症・進展にどのような影響を与えるのかを検討する。そして、この因子を標的とした新たな治療法の開発につなげる。

Outline of Final Research Achievements

Diabetic kidney disease (DKD) is a leading cause of end stage renal disease. In the present study we demonstrated that ROCK2, an effector of small G protein Rho, induces glomerular endothelial and epithelial dysfunction, resulting in the development of DKD. ROCK2 could be an important therapeutic target of DKD.

Academic Significance and Societal Importance of the Research Achievements

糖尿病患者の末期腎不全への進展抑制は患者の生命予後改善のみならず医療経済的にも重要な課題である。糖尿病性腎臓病は現在のところ血糖、血圧、脂質といったリスクファクターの管理に大きく依存しており、成因の解明とそれに応じた治療法の開発が求められている。本研究ではROCK2が腎糸球体において内皮細胞機能および上皮細胞機能障害を誘導し、糖尿病性腎臓病の発症・進展を抑制することを明らかにした。ROCK2阻害薬は臨床応用に向けて開発が進んでおり、新たな糖尿病性腎臓病治療薬としての可能性が期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 14 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] ROCK2-induced metabolic rewiring in diabetic podocytopathy2022

    • Author(s)
      Matoba Keiichiro、Takeda Yusuke、Nagai Yosuke、Sekiguchi Kensuke、Ukichi Rikako、Takahashi Hiroshi、Aizawa Daisuke、Ikegami Masahiro、Tachibana Toshiaki、Kawanami Daiji、Kanazawa Yasushi、Yokota Tamotsu、Utsunomiya Kazunori、Nishimura Rimei
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 341-341

    • DOI

      10.1038/s42003-022-03300-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Bone-Derived Hormones in Glucose Metabolism, Diabetic Kidney Disease, and Cardiovascular Disorders2022

    • Author(s)
      Takashi Yuichi、Kawanami Daiji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 4 Pages: 2376-2376

    • DOI

      10.3390/ijms23042376

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease2021

    • Author(s)
      Kawanami Daiji、Takashi Yuichi、Muta Yoshimi、Oda Naoki、Nagata Dai、Takahashi Hiroyuki、Tanabe Makito
    • Journal Title

      Frontiers in Pharmacology

      Volume: 12 Pages: 754239-754239

    • DOI

      10.3389/fphar.2021.754239

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FGF23 and Hypophosphatemic Rickets/Osteomalacia2021

    • Author(s)
      Takashi Yuichi、Kawanami Daiji、Fukumoto Seiji
    • Journal Title

      Current Osteoporosis Reports

      Volume: 19 Issue: 6 Pages: 669-675

    • DOI

      10.1007/s11914-021-00709-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eating Speed and Incidence of Diabetes in a Japanese General Population: ISSA-CKD.2021

    • Author(s)
      Fujii H, Funakoshi S, Maeda T, Satoh A, Kawazoe M, Ishida S, Yoshimura C, Yokota S, Tada K, Takahashi K, Ito K, Yasuno T, Okutsu S, Mukoubara S, Nakashima H, Nabeshima S, Kondo S, Fujita M, Masutani K, Arima H, Kawanami D.
    • Journal Title

      J Clin Med.

      Volume: 10 Issue: 9 Pages: 1949-1949

    • DOI

      10.3390/jcm10091949

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Renoprotective Effects of DPP-4 Inhibitors2021

    • Author(s)
      Kawanami Daiji、Takashi Yuichi、Takahashi Hiroyuki、Motonaga Ryoko、Tanabe Makito
    • Journal Title

      Antioxidants

      Volume: 10 Issue: 2 Pages: 246-246

    • DOI

      10.3390/antiox10020246

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Journal Article] Pemafibrate, a PPAR alpha agonist, attenuates neointima formation after vascular injury in mice fed normal chow and a high-fat diet2020

    • Author(s)
      Horikawa Tsuyoshi、Kawanami Takako、Hamaguchi Yuriko、Tanaka Yuki、Kita Shotaro、Ryorin Ryutaro、Takashi Yuichi、Takahashi Hiroyuki、Tanabe Makito、Yanase Toshihiko、Kawanami Daiji、Nomiyama Takashi
    • Journal Title

      Heliyon

      Volume: 6 Issue: 11 Pages: e05431-e05431

    • DOI

      10.1016/j.heliyon.2020.e05431

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ROCK Inhibition May Stop Diabetic Kidney Disease2020

    • Author(s)
      Keiichiro Matoba, Yusuke Takeda, Yosuke Nagai, Yasushi Kanazawa , Daiji Kawanami, Tamotsu Yokota, Kazunori Utsunomiya, Rimei Nishimura
    • Journal Title

      JMA Journal

      Volume: 3 Issue: 3 Pages: 154-163

    • DOI

      10.31662/jmaj.2020-0014

    • NAID

      130007905816

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Medical nutrition therapy and dietary counseling for patients with diabetes-energy, carbohydrates, protein intake and dietary counseling2020

    • Author(s)
      Yamauchi Toshimasa、Kamiya Hideki、Utsunomiya Kazunori、Watada Hirotaka、Kawanami Daiji、Sato Junko、Kitada Munehiro、Koya Daisuke、Harada Norio、Shide Kenichiro、Joo Erina、Suzuki Ryo、Bouchi Ryotaro、Ohta Yasuharu、Kondo Tatsuya
    • Journal Title

      Diabetology International

      Volume: 11 Issue: 3 Pages: 224-239

    • DOI

      10.1007/s13340-020-00437-7

    • NAID

      130007821841

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Clinical Outcomes to Mechanisms2020

    • Author(s)
      Kawanami Daiji、Takashi Yuichi
    • Journal Title

      Frontiers in Pharmacology

      Volume: 11 Pages: 967-967

    • DOI

      10.3389/fphar.2020.00967

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of Metformin Use in Diabetic Kidney Disease2020

    • Author(s)
      Kawanami Daiji、Takashi Yuichi、Tanabe Makito
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 12 Pages: 4239-4239

    • DOI

      10.3390/ijms21124239

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation2020

    • Author(s)
      Komatsu Shiho、Nomiyama Takashi、Numata Tomohiro、Kawanami Takako、Hamaguchi Yuriko、Iwaya Chikayo、Horikawa Tsuyoshi、Fujimura-Tanaka Yuki、Hamanoue Nobuya、Motonaga Ryoko、Tanabe Makito、Inoue Ryuji、Yanase Toshihiko、Kawanami Daiji
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 1 Pages: 99-106

    • DOI

      10.1507/endocrj.EJ19-0428

    • NAID

      130007790952

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ROCK2 Regulates Monocyte Migration and Cell to Cell Adhesion in Vascular Endothelial Cells.2019

    • Author(s)
      Takeda Y, Matoba K, Kawanami D, Nagai Y, Akamine T, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 6 Pages: 1331-1331

    • DOI

      10.3390/ijms20061331

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease2019

    • Author(s)
      Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease
    • Journal Title

      10.3390/ijms20143393

      Volume: 20 Issue: 14 Pages: 3393-3393

    • DOI

      10.3390/ijms20143393

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ROCK2 regulates TGF-β-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in mesangial cells2019

    • Author(s)
      Yosuke Nagai, Keiichiro Matoba, Daiji Kawanami, Yusuke Takeda, Tomoyo Akamine, Sho Ishizawa, Yasushi Kanazawa, Tamotsu Yokota, Kazunori Utsunomiya, Rimei Nishimura
    • Journal Title

      American Journal of Physiology Renal Physiology

      Volume: 317 Issue: 4 Pages: 839-851

    • DOI

      10.1152/ajprenal.00596.2018

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycolaldehyde induces sensory neuron death through activation of the c-Jun N-terminal kinase and p-38 MAP kinase pathways.2019

    • Author(s)
      Akamine T, Takaku S, Suzuki M, Niimi N, Yako H, Matoba K, Kawanami D, Utsunomiya K, Nishimura R, Sango K
    • Journal Title

      Histochemistry and cell biology

      Volume: 153 Issue: 2 Pages: 111-119

    • DOI

      10.1007/s00418-019-01830-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 糖尿病性腎臓病におけるリン代謝、FGF23とRho-kinaseの関与2021

    • Author(s)
      川浪大治
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Annual Research Report
    • Invited

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Published: 2019-04-18   Modified: 2023-01-30  

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