Rapamycin Attenuated Podocyte Apoptosis Via Upregulation of Nestin in Ang II-Induced Podocyte Injury

DOI: https://doi.org/10.21203/rs.3.rs-708190/v1

Abstract

Background: Angiotensin II (Ang II) contributes to the progression of glomerulosclerosis mainly by inducing podocyte injury. Convincing evidence indicates that the mTOR inhibitor rapamycin plays a fundamental role in the protection of podocyte injury. Nestin, a major cytoskeleton protein, is expressed stably in podocytes and correlates with podocyte damage. The purpose of this study was to investigate the effect of rapamycin in podocyte injury induced by Ang II, and clarify the role and mechanism of Nestin in the protection of podocyte injury.

Methods and Results: We established an Ang II perfusion animal model, and the effects of interfere treatment of rapamycin on podocyte were detected in vivo. In vitro, podocytes were stimulated with Ang II and rapamycin to observe podocyte injury, nestin-siRNA was transfected to investigate the mechanism in the process. We observed that Ang II induce podocyte injury both in vivo and in vitro, while rapamycin treatment relieved Ang II-induced podocyte injury. Also we found that nestin co-localized with p-mTOR in glomeruli, and the protection effect of rapamycin was reduced by nestin-siRNA in podocytes. Moreover, co-IP indicated the interaction between nestin and p-mTOR, and nestin could affect podocyte injury via mTOR/P70S6K signaling pathway.

Conlusion: Thus, here, we demonstrated that Rapamycin attenuated podocyte apoptosis via upregulation of nestin through mTOR/P70S6K signsling pathway in Ang II-induced podocyte injury.

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