Progression of podocyte disease

• Project/Area Number: 17K09685
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Nagata Michio 筑波大学, 医学医療系, 教授 (10192238)
• Project Period (FY): 2017-04-01 – 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 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ポドサイト / 糸球体硬化 / 糸球体ろ過 / 剥離 / 壁細胞 / ろ過 / 糸球体濾過 / CD44 / ケモカイン / NEP25 / 慢性腎臓病 / インテグリン

Outline of Final Research Achievements

We performed two sets of experiments using podocyte selective toxin model.
1.Electron microscopically mapping of podocyte injury/detachment showed glomerular pathophysiology, including filtrate and anatomical characteristics of glomerular position and structures is prerequisite for podocyte detachment and segmental sclerosis. 2.Injured podocyte expressed cell migration-driving chemokines, MIF and SDF1, which stimulate migration of parietal cells by expressing their common receptor, CXCR4 chemokines. After podocyte detachment, autocrine mechanism of chemokines and their receptor in PEC promote segmental sclerosis after podocyte loss.

Academic Significance and Societal Importance of the Research Achievements

ポドサイト研究は慢性腎臓病CKDの共通のメカニズムとして広く知られており、本研究はポドサイト障害と糸球体クオカとの因果関係についてびょうりがくてきに、その特性と背景分枝かを明らかにしたものである。このポドサイト特異的障害モデルを用いた2つの研究は、大変ユニークであり、CKDの機序を理解することに貢献したと考えている。

Research Products

• [Journal Article] Biphasic MIF and SDF1 expression during podocyte injury promote CD44-mediated glomerular parietal cell migration in focal segmental glomerulosclerosis (2020)
  • Author(s): Ito N, Sakamoto K, Hikichi C, Matsusaka T, Nagata M.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 318 Issue: 3 Pages: F741-F753
  • DOI: 10.1152/ajprenal.00414.2019
  • Peer Reviewed
• [Presentation] ポドサイト障害と分節性硬化 (2019)
  • Author(s): 井藤奈央子、坂本和雄、長田道夫
  • Organizer: 日本腎臓学会
• [Presentation] Glomerular filtrate determines podocyte detachment in diffuse podocyte injury. (2019)
  • Author(s): Saga N, Nagata M
  • Organizer: American Society of Nephrology
  • Int'l Joint Research
• [Presentation] ポドサイト障害と剥離機構の検討 (2018)
  • Author(s): 佐賀信之、井藤奈央子、坂本和雄、長田道夫
  • Organizer: 第2回ポドサイト研究会