Abstract
Abstract
Objectives
Renal fibrosis (RF) is a critical pathway in the progression of chronic kidney disease (CKD) to end-stage kidney diseases. This study aimed to investigate the role of miR-101-3p in the progression of fibrosis in renal tubular epithelial cells (RTECs) and to elucidate the underlying molecular mechanisms.
Methods
An RF cell model was established by induction with transforming growth factor-β1 (TGF-β1). The expression levels of miR-101-3p and fibrosis-associated proteins were measured using quantitative real-time reverse transcription polymerase chain reaction. Cell migration ability was detected by Transwell assay. The potential target genes of miR-101-3p were predicted through bioinformatic analysis. The interaction between miR-101-3p and EZH2 was verified using the luciferase assay and RNA immunoprecipitation (RIP) assay.
Results
HK-2 cells treated with TGF-β1 showed downregulated expression of miR-101-3p. Overexpression of miR-101-3p reduced cell migration and decreased the production of fibronectin, collagen IV and α-smooth muscle actin (α-SMA). EZH2 was identified as a downstream target gene of miR-101-3p. The interaction between miR-101-3p and EZH2 was confirmed by luciferase assay and RIP assay. EZH2 was upregulated in TGF-β1-induced cells. Upregulation of EZH2 partially reversed the anti-fibrotic effects caused by miR-101-3p overexpression.
Conclusions
miR-101-3p alleviates TGF-β1-induced fibrosis in RTECs by inhibiting EZH2. This study provides new insights into the molecular mechanisms of RF and suggests potential therapeutic targets for CKD.