Development of Vasohibin-2-targeting theray against chronic kidney disease

• Project/Area Number: 18K08210
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Okayama University
• Principal Investigator: Tanabe Katsuyuki 岡山大学, 大学病院, 助教 (40534805)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 慢性腎臓病 / ポドサイト / 腎線維化 / Vasohibin / 蛋白尿 / 糖尿病性腎症 / 血管新生

Outline of Final Research Achievements

In this study, we examined the effects of imbalance between Vasohibin-1 and Vasohibin-2 expression in kidney diseases. Based on our animal experiments, Vasohibin-1 regulated detyrosination of microtubule α-tubulin in podocytes and was involved in the maintenance of glomerular filtration barrier. In addition, Vasohibin-2 deficiency promoted inflammatory infiltration in the kidney during acute injury processes. Taken together, this study demonstrated that Vasohibin-1 and Vasohibin-2 expression could be novel therapeutic target in kidney diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究は未だ有効な治療法が確立されていない糖尿病性腎症や腎線維化のような病態において、血管の形態・機能の制御にかかわる新たな蛋白質であるVasohibin-1とVasohibin-2の発現の不均衡が及ぼす影響を検討した。Vasohibinは微小管蛋白の修飾に関与することが知られているが、腎臓ではVasohibin-1がポドサイトでその役割を担うことを示した。また、Vasohibin-2の欠乏は急性の腎障害において炎症を増強させることを示し、Vasohibin-1とVasohibin-2の発現が腎疾患の治療の標的となる可能性が証明された。

Research Products

• [Journal Article] Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury (2020)
  • Author(s): Miyake Hiromasa、Tanabe Katsuyuki、Tanimura Satoshi、Nakashima Yuri、Morioka Tomoyo、Masuda Kana、Sugiyama Hitoshi、Sato Yasufumi、Wada Jun
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 12 Pages: 4545-4545
  • DOI: 10.3390/ijms21124545
  • NAID: 120006872424
  • Peer Reviewed / Open Access
• [Journal Article] Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model (2019)
  • Author(s): Tanimura Satoshi、Tanabe Katsuyuki、Miyake Hiromasa、Masuda Kana、Tsushida Keigo、Morioka Tomoyo、Sugiyama Hitoshi、Sato Yasufumi、Wada Jun
  • Journal Title: American Journal of Physiology-Renal Physiology Volume: 317 Issue: 2 Pages: F264-F274
  • DOI: 10.1152/ajprenal.00045.2019
  • Peer Reviewed / Open Access
• [Journal Article] Endogenous Antiangiogenic Factors in Chronic Kidney Disease: Potential Biomarkers of Progression (2018)
  • Author(s): Tanabe Katsuyuki、Sato Yasufumi、Wada Jun
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 7 Pages: 1859-1859
  • DOI: 10.3390/ijms19071859
  • Peer Reviewed / Open Access
• [Presentation] Vasohibin-1及び2を標的とした糖尿病性腎症の治療戦略 (2021)
  • Author(s): 田邊克幸
  • Organizer: 第15回Vasohibin研究会
• [Presentation] 腎疾患の進行におけるVasohibinの役割 (2020)
  • Author(s): 田邊克幸
  • Organizer: 第43回日本分子生物学会
• [Presentation] Vasohibin-1 has α-tubulin detyrosinating activity in podocytes (2020)
  • Author(s): Morioka T, Tanabe K, Tanimura S, Sugiyama H, Sato Y, WadaJ
  • Organizer: The 9th Chronic Kidney Disease Frontier Meeting
  • Int'l Joint Research
• [Presentation] vasohibin-1はポドサイトにおける微小管α-tubulinの脱チロシン化を制御する (2019)
  • Author(s): 森岡朋代, 田邊克幸, 谷村智史, 杉山斉, 佐藤靖史, 和田淳
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] Vasohibin-1 is essential for the post-transcriptional modification of α-tubulin on microtubules in podocytes (2019)
  • Author(s): Morioka T, Tanabe K, Tanimura S, Sugiyama H, Wada J
  • Organizer: American Society of Nephrology Kidney Week 2019
  • Int'l Joint Research
• [Presentation] 慢性腎臓病の進行における腎Vasohibin発現の関与の解明 (2019)
  • Author(s): 田邊克幸
  • Organizer: 第14回Vasohibin研究会