UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability

作者：Wei Xiong, Zhiyong Xiong, Anni Song, Chun‐Tao Lei, Chen Ye, Hua Su, Chun Zhang · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04376-0 · 被引用次数：30 · 研究领域：Chronic Kidney Disease and Diabetes、Adipose Tissue and Metabolism、Bladder and Urothelial Cancer Treatments

BACKGROUND: Renal interstitial fibrosis is a common pathway for the progressive development of chronic renal diseases (CKD) with different etiology, and is the main pathological basis leading to end-stage renal disease. Although the current research on renal interstitial fibrosis is gradually deepening, the diagnosis and treatment methods are still very lacking. Uncoupling protein 1 (UCP1) is a nuclear encoded protein in mitochondria inner membrane and plays an important role in regulating energy metabolism and mitochondrial homeostasis. However, the biological significance of UCP1 and potential regulatory mechanisms in the development of CKD remain unclear. METHODS: Unilateral ureteral obstruction (UUO) model was used to construct the animal model of renal fibrosis, and TGF-β1 stimulation of HK2 cells was used to construct the vitro model of renal fibrosis. UCP1 expression was detected by Western blot, immunoblot analysis and immunohistochemistry. UCP1 was upregulated by UCP1 overexpressing lentivirus and UCP1 agonist CL316243. Western blot and immunofluorescence were used to detect epithelial mesenchymal transition (EMT)-related markers, such as collagen I, fibronectin, antioxidant enzyme SOD2 and CAT. Reactive oxygen species (ROS) production was detected by ROS detection kit. SIRT3 knockdown was performed by siRNA. RESULTS: This study presents that UCP1 is significantly downregulated in patients with renal fibrosis and UUO model. Further studies discover that UCP1 overexpr...