PGC-1α ameliorates kidney fibrosis in mice with diabetic kidney disease through an antioxidative mechanism

Zhang,Liwen; Liu,Jian; Zhou,Fangfang; Wang,Weiming; Chen,Nan

doi:10.3892/mmr.2018.8433

PGC-1α ameliorates kidney fibrosis in mice with diabetic kidney disease through an antioxidative mechanism

Authors:
- Liwen Zhang
- Jian Liu
- Fangfang Zhou
- Weiming Wang
- Nan Chen
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Affiliations: Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
Published online on: January 16, 2018 https://doi.org/10.3892/mmr.2018.8433
Pages: 4490-4498
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The production of reactive oxygen species (ROS) is a common phenomenon in podocyte impairment, which leads to the irreversible progression of chronic kidney diseases, such as diabetic kidney disease (DKD). Previous research has indicated that peroxisome proliferator‑activated receptor γ (PPARγ) coactivator‑1α (PGC‑1α) participates in mitochondrial biogenesis and energy metabolism in certain mitochondria‑enriched cells, including myocardial and skeletal muscle cells. Therefore, we hypothesized that PGC‑1α may be a protective nuclear factor against energy and oxidative stress in DKD. To investigate this hypothesis, db/db diabetic mice were used to establish a DKD model and the PPARγ agonist rosiglitazone was employed to induce PGC‑1α expression in vivo. Additionally, immortalized mouse podocytes and SV40 MES 13 renal mesangial cells were utilized for in vitro experiments. The expression levels of PGC‑1α and genes associated with kidney and cell injury were determined by western blotting or reverse transcription-quantitative polymerase chain reaction and intracellular ROS levels were assessed by 2',7'-dichlorodihydrofluorescein diacetate. The results of the present study demonstrated that endogenous PGC‑1α expression exhibited protective effects against oxidative stress, glomerulosclerosis and tubulointerstitial fibrosis in experimental DKD. These results indicated a potential role of PGC‑1α in the amelioration of key pathophysiological features of DKD and provided evidence for PGC‑1α as a potential therapeutic target in DKD.

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