Elucidation of the pathogenesis and development of new diagnostic and therapeutic strategy of kidney disease based on mechanobiology

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08616
• 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: Kyorin University
• Principal Investigator: NAGASE Miki 杏林大学, 医学部, 教授 (60302733)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: メカノバイオロジー / Piezo2 / メサンギウム細胞 / 傍糸球体レニン産生細胞 / 血管外膜線維芽細胞 / 急性腎障害 / 慢性腎臓病 / 高血圧性腎障害

Outline of Final Research Achievements

Kidney cells are exposed to various mechanical stimuli caused by blood flow, blood pressure, and urinary flow, but their sensing and response mechanisms remain largely elusive. In this study, we focused on the mechanosensor molecule Piezo2, and found that in the normal kidney, Piezo2 expression was restricted to the glomerular mesangial cells and juxtaglomerular renin-producing cells. In the developing metanephros, Piezo2 was expressed in the Foxd1-positive mesenchymal progenitor cells and their lineage cells. In dehydration mice, its expression was decreased in the mesangial cells, while increased in the renin cells. In hypertensive nephrosclerosis models with glomerular hypertension, Piezo2 expression was enhanced in the mesangial cells, some renin-producing cells, and perivascular collagen-producing cells, which was normalized by antihypertensive treatment with mineralocorticoid receptor antagonist. These results suggest the role of Piezo2 in the pathogenesis of kidney diseases.

Free Research Field

腎臓病学

Academic Significance and Societal Importance of the Research Achievements

糖尿病・高血圧などを発症基盤とする慢性腎臓病（CKD）や、救急医療や集中治療室患者で頻度の高い急性腎障害（AKI）は、患者の生命予後やQOLに大きく影響する疾患であるが、未だ有効な治療法がない。現在Piezo2阻害の影響を解析しているが、メカノ感受応答システムの入り口にあたるメカノセンサーPiezo2は、腎臓病治療法の新たな標的として有望と考えられる。CKDやAKIに対し、病態に基づく特効薬が開発されれば、透析を必要としない健康な長寿社会が期待される。