Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, 262 Zhongshan North Road, Nanjing, 210003, Jiangsu Province, China.
Mol Biol Rep. 2022 Mar;49(3):2119-2128. doi: 10.1007/s11033-021-07029-x. Epub 2022 Feb 11.
Angiotensin II (Ang II) contributes to the progression of glomerulosclerosis, mainly by inducing podocyte injury. Convincing evidence indicates that the mTOR inhibitor rapamycin could play a fundamental role in protection against podocyte injury. Nestin, a major cytoskeletal protein, is stably expressed in podocytes and correlates with podocyte damage. The purpose of this study was to investigate the effect of rapamycin on podocyte injury induced by Ang II and to clarify the role and mechanism of nestin in the protective effect of rapamycin of podocyte injury.
We established an Ang II perfusion animal model, and the effects of rapamycin treatment on podocytes were investigated in vivo. In vitro, podocytes were stimulated with Ang II and rapamycin to observe podocyte injury, and nestin-siRNA was transfected to investigate the underlying mechanisms. We observed that Ang II induced podocyte injury both in vivo and in vitro, whereas rapamycin treatment relieved Ang II-induced podocyte injury. We further found that nestin co-localized with p-mTOR in glomeruli, and the protective 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 the mTOR/P70S6K signaling pathway.
We demonstrated that rapamycin attenuated podocyte apoptosis via upregulation of nestin expression through the mTOR/P70S6K signaling pathway in an Ang II-induced podocyte injury.
血管紧张素 II（Ang II）通过诱导足细胞损伤促进肾小球硬化的进展。有充分证据表明，mTOR 抑制剂雷帕霉素可能在防止足细胞损伤方面发挥重要作用。巢蛋白是一种主要的细胞骨架蛋白，在足细胞中稳定表达，并与足细胞损伤相关。本研究旨在探讨雷帕霉素对 Ang II 诱导的足细胞损伤的作用，并阐明巢蛋白在雷帕霉素保护足细胞损伤中的作用和机制。
我们建立了 Ang II 灌注动物模型，研究了雷帕霉素处理对体内足细胞的影响。在体外，用 Ang II 和雷帕霉素刺激足细胞，观察足细胞损伤，并用巢蛋白-siRNA 转染来探讨潜在的机制。我们观察到 Ang II 诱导了体内和体外的足细胞损伤，而雷帕霉素处理缓解了 Ang II 诱导的足细胞损伤。我们进一步发现巢蛋白与肾小球中的 p-mTOR 共定位，并且巢蛋白-siRNA 降低了雷帕霉素在足细胞中的保护作用。此外，Co-IP 表明巢蛋白和 p-mTOR 之间存在相互作用，并且巢蛋白可以通过 mTOR/P70S6K 信号通路影响足细胞损伤。
我们证明了雷帕霉素通过上调巢蛋白表达来减轻 Ang II 诱导的足细胞损伤，这是通过 mTOR/P70S6K 信号通路实现的。
