Ang-(1-7) attenuates podocyte injury induced by high glucose in vitro

• Published in: Archives of Endocrinology and Metabolism Vol. 67; no. 6; p. e000643
• Main Authors: Lu, Jianxin, Chen, Guixiang, Shen, Guanghui, Ouyang, Wenhao
• Format: Journal Article
• Language: English
• Published: Brazil Brazilian Society of Endocrinology and Metabolism 19.06.2023
• Subjects: Ang-(1-7); Angiotensin II - pharmacology; Animals; Diabetic Nephropathies; diabetic nephropathy; Glucose - pharmacology; Mas; Mice; podocyte; Podocytes - metabolism; Podocytes - pathology; Renin angiotensin system (RAS); Renin angiotensin system (RAS); Ang-(1-7); Mas; diabetic nephropathy; podocyte
• ISSN: 2359-3997; 2359-4292
• DOI: 10.20945/2359-3997000000643

The incidence of diabetic nephropathy (DN) is gradually increasing worldwide. Podocyte injury, such as podocyte apoptosis and loss of the slit diaphragm (SD)-specific markers are early pathogenic features of DN. The cultured mouse podocytes were separated into a high glucose-treated (HG, 30mM) group to mimic DN , a low glucose-treated (LG, 5mM) group as a control and HG+ angiotensin-(1-7)(Ang-(1-7)) and HG+Ang-(1-7) + D-Ala7-Ang-(1-7) (A779, Ang-(1-7)/Mas receptor antagonist) experimental groups. The Cell Counting Kit-8 (CCK-8) method and flow cytometry was used to detect podocyte activity and podocyte apoptosis respectively. The expression of angiotensin type 1 receptor (AT1R), Mas receptor (MasR) and podocyte-specific markers were examined by q-PCR and Western blot, respectively. The results showed that the decrease in podocyte activity; the increase in podocyte apoptosis; the decreased mRNA and protein expression of nephrin, podocin, WT-1 and MasR; and the upregulated expression of AT1R induced by HG could be reversed by Ang-(1-7). However, these effects were blocked by A779. The possible mechanisms of the Ang-(1-7)-mediated effect depended on MasR. In addition, the protective effect of Ang-(1-7) on podocyte activity was dose-dependent and most obvious at 10 µM. A779 had the greatest antagonistic action against Ang-(1-7) at a concentration of 10 μM. This study reveals that binding of Ang-(1-7) to its specific receptor MasR may counteract the effects of Ang II mediated by AT1R to significantly attenuate podocyte injury induced by high glucose. Ang-(1-7)/MasR targeting in podocytes may be a therapeutic approach to attenuate renal injury in DN.