Knockdown of miR-214 Alleviates Renal Interstitial Fibrosis by Targeting the Regulation of the PTEN/PI3K/AKT Signalling Pathway

The microRNA-214 (miR-214) precursor is formed by the DNM3 gene on human chromosome 1q24.3, which is encoded and transcribed in the nucleus and processed into mature miR-214 in the cytoplasm. Association of miR-214 with the interstitial fibrosis of the kidney has been reported in existing research. Renal interstitial fibrosis is considered necessary during the process of various renal injuries in chronic kidney disease (CKD). One of the important mechanisms is the TGF- (transforming growth factor-) beta 1-stimulated epithelial interstitial transformation (EMT). The specific mechanisms of miR-214-3p in renal interstitial fibrosis and whether it participates in EMT are worthy of further investigation. In this paper, we first demonstrated modulation of the downstream PI3K/AKT axis by miR-214-3p through targeting phosphatase and tension protein homologues (PTEN), indicating the miRNA's participation in unilateral ureteral obstruction (UUO) nephropathy and TGF-beta 1-induced EMT. We overexpressed or silenced miR-214-3p and PTEN for probing into the correlation of miR-214-3p with PTEN and the downstream PI3K/AKT signalling pathways. According to the results of the study, miR-214-3p overexpression silenced PTEN, activated the PI3K/AKT signalling pathway, and exacerbated EMT induced by TGF-beta 1, while miR-214-3p knockdown had the opposite effect. In miR-214-3p knockdown mice, the expression of PTEN was increased, the PI3K/AKT signalling pathway was inhibited, and fibrosis was alleviated. In conclusion, miR-214-3p regulates the EMT of renal tubular cells induced by TGF-beta 1 by targeting PTEN and regulating the PI3K/AKT signalling pathway. Furthermore, miR-214-3p knockdown can reduce renal interstitial fibrosis through the PTEN/PI3K/AKT pathway.