2021 Fiscal Year Final Research Report
Pathophysiological significance of angiotensin receptor-binding protein in leucocytes and immune cells
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。
|