Regulation of Endothelial Function by mDia1

• Project/Area Number: 16K09523
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Fukuoka University (2019); Jikei University School of Medicine (2016-2018)
• Principal Investigator: Kawanami Daiji 福岡大学, 医学部, 教授 (50568889)
• Co-Investigator(Kenkyū-buntansha): 宇都宮 一典 東京慈恵会医科大学, 医学部, 教授 (50185047)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 動脈硬化 / 血管内皮機能 / Rho / mDia1 / Rho-kinase / 血管内皮

Outline of Final Research Achievements

Atherosclerosis is known to occur due to vascular endothelial dysfunction. This study focused on mDia1 as a factor that regulates vascular endothelial function. mDia1 is an effector located downstream of small G protein Rho. Rho-kinase is known as an effector of Rho in addition to mDia1. We hypothesized that Rho-kinase and mDia1 interact with each other to regulate vascular endothelial function. We performed experimental studies using mice and cultured cells in which the endothelial ROCK2 isoform of Rho-kinase was deficient. It was revealed that mDia1 does not play a major role in the regulation of vascular endothelial function.

Academic Significance and Societal Importance of the Research Achievements

低分子量GタンパクRhoに関連するシグナルとしては、動脈硬化の治療標的としてmDia1よりもROCK2がふさわしいことが明らかになった。今後はROCK2を標的とした創薬を行うことが動脈硬化治療における新たな戦略となり得る可能性が示された。

Research Products

• [Journal Article] SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation (2020)
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease (2019)
  • 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
  • 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 cells (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of a myelinating co-culture system with a motor neuron-like cell line NSC-34 and an adult rat Schwann cell line IFRS1. (2018)
  • Author(s): Takaku S, Yako H, Niimi N, Akamine T, Kawanami D, Utsunomiya K, Sango K.
  • Journal Title: Histochem Cell Biol Volume: 印刷中 Issue: 5 Pages: 537-543
  • DOI: 10.1007/s00418-018-1649-x
  • Peer Reviewed
• [Journal Article] SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy. (2017)
  • Author(s): Kawanami D, Matoba K, Takeda Y, Nagai Y, Akamine T, Yokota T, Sango K, Utsunomiya K.
  • Journal Title: Int J Mol Sci Volume: 18 Issue: 5 Pages: 1083-1083
  • DOI: 10.3390/ijms18051083
  • Peer Reviewed / Open Access
• [Journal Article] Rho-Kinase Blockade Attenuates Podocyte Apoptosis by Inhibiting the Notch Signaling Pathway in Diabetic Nephropathy. (2017)
  • Author(s): Matoba K, Kawanami D, Nagai Y, Takeda Y, Akamine T, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K.
  • Journal Title: Int J Mol Sci Volume: 18 Issue: 8 Pages: 1795-1795
  • DOI: 10.3390/ijms18081795
  • Peer Reviewed / Open Access
• [Journal Article] Incretin-based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence. (2016)
  • Author(s): Daiji Kawanami, Keiichiro Matoba, Kazunori Sango, Kazunori Utsunomiya
  • Journal Title: International Journal of Molecular Medicine Volume: 17 Issue: 8 Pages: 1223-1223
  • DOI: 10.3390/ijms17081223
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Signaling pathways in diabetic nephropathy (2016)
  • Author(s): Daiji Kawanami, Keiichiro Matoba, Kazunori Utsunomiya
  • Journal Title: Histology and Histopathology Volume: 31 Pages: 1059-1067
  • Peer Reviewed / Acknowledgement Compliant