Pathophysiological significance of angiotensin receptor-binding protein in leucocytes and immune cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17575
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Yokohama City University
• Principal Investigator: UNEDA Kazushi 横浜市立大学, 医学研究科, 客員研究員 (90780370)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: レニン・アンジオテンシン系 / ATRAP / 1型アンジオテンシン受容体

Outline of Final Research Achievements

ATRAP deficient mice exhibited an exacerbation of streptozotocin-induced diabetic glomerular injury compared to wild-type control mice. These phenomena were accompanied by decreased expression of CD206, a marker of alternatively activated and tissue-reparative M2 macrophages, in the kidney tubulointerstitium. There were no significant differences in the expression levels of M2 macrophage-related genes and CD206 in IL-10– and TGF-b–incubated bone marrow–derived macrophages from wild-type mice and ATRAP deficient mice. Additionally, adoptive transfer of M2- polarized macrophages into diabetic ATRAP-knockout mice ameliorated the glomerular injury. These results indicates that ATRAP-M2 macrophages axis is a therapeutic target for diabetic kidney diseases.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症に対するレニン－アンジオテンシン（RA）系阻害の腎保護効果の新たなメカニズムとして，腎尿細管RA系の過剰な活性化が，マクロファージの極性変化を介して糸球体障害を増悪させるという腎尿細管－マクロファージー糸球体連関の存在を新たに示した。糖尿病性腎症において既存薬によるRA系の過度な抑制は，むしろ副作用が増えることことが報告されているため，RA系の生理的シグナルには悪影響を与えずに，臓器障害と関連したシグナルのみ選択的に抑制できるATRAP-M2マクロファージ軸が，糖尿病性腎症の新たな治療標的となる可能性がある。