Hypermethylation and suppression of microRNA219a-2 activates the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis.

ABSTRACT: Epigenetic regulations, such as DNA methylation and microRNAs, play an important role in renal fibrosis. Here, we report the regulation of microRNA219a-2 by DNA methylation in fibrotic kidneys, unveiling the crosstalk between these epigenetic mechanisms. Through genome-wide DNA methylation analysis and pyrosequencing, we detected the hypermethylation of microRNA219a-2 in renal fibrosis induced by unilateral ureteral obstruction (UUO) or renal ischemia/reperfusion, which was accompanied by a significant decrease in microRNA-219a-5p expression. Functionally, overexpression of microRNA219a-2 enhanced fibronectin induction during hypoxia or TGF-β1 treatment of cultured renal cells. In mice, inhibition of microRNA-219a-5p suppressed fibronectin accumulation in UUO and ischemic/reperfused kidney

SUBMITTER: Wei Q 

PROVIDER: S-EPMC11764320 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature