Sestrin‑2 regulates podocyte mitochondrial dysfunction and apoptosis under high‑glucose conditions via AMPK

Lin,Qiaoxuan; Ma,Yiqiong; Chen,Zhaowei; Hu,Jijia; Chen,Cheng; Fan,Yanqin; Liang,Wei; Ding,Guohua

doi:10.3892/ijmm.2020.4508

Sestrin‑2 regulates podocyte mitochondrial dysfunction and apoptosis under high‑glucose conditions via AMPK

Authors:
- Qiaoxuan Lin
- Yiqiong Ma
- Zhaowei Chen
- Jijia Hu
- Cheng Chen
- Yanqin Fan
- Wei Liang
- Guohua Ding
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Affiliations: Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: February 20, 2020 https://doi.org/10.3892/ijmm.2020.4508
Pages: 1361-1372
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic kidney disease (DKD) is a severe form of microangiopathy among diabetic patients, of which podocyte injury is one of the more predominant features. There is increasing evidence to suggest that mitochondrial dysfunction is associated with podocyte injury, thus contributing to the progression of DKD. Initially identified as a p53 target protein, the endogenous antioxidant protein, sestrin‑2 (sesn2), has recently attracted attention due to its potential function in various inflammatory diseases. However, the association between sesn2 and podocytes in DKD remains unclear. In the present study, to elucidate the role of sesn2 in podocyte mitochondrial dysfunction, the effects of sesn2 on the regulation of AMP‑activated protein kinase (AMPK) were examined in vitro and in vivo. Abnormal mitochondria were found in rats with streptozotocin‑induced diabetes, and hyperglycemia downregulated the expression of sesn2. The upregulation of sesn2 increased the level of AMPK phosphorylation, and thus ameliorated mitochondrial dysfunction under high glucose conditions (HG). On the whole, these results suggest that sesn2 is associated with mitochondrial dysfunction in podocytes under HG conditions. In addition, the decreased expression of sesn2 may be a therapeutic target for DKD.

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