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

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.