Microvesicle-containing miRNA-153-3p induces the apoptosis of proximal tubular epithelial cells and participates in renal interstitial fibrosis

OBJECTIVE: To uncover the role of microvesicle-containing (MV-containing) miRNA-153-3p in inducing the apoptosis of proximal tubular epithelial cells and RIF (renal interstitial fibrosis), and its potential mechanism. MATERIALS AND METHODS: Mice were subjected to unilateral ureteral obstruction (UUO) to establish the in vivo RIF model. MVs were extracted from the obstructed kidney tissues of mice, to further isolate the RNAs. MiRNA-153-3p levels in RIF mice and MVs were determined. In vitro RIF model was constructed by TGF-beta 1 induction in NRK-52E and NRK-49F cells. The regulatory effect of miRNA-153-3p on the apoptosis of tubular epithelial cells was examined. Subsequently, potential target gene of miRNA-153-3p was predicted and identified. Rescue experiments were finally carried out to uncover the role of miRNA-153-3p/Bcl-2 in influencing RIF. RESULTS: MiRNA-153-3p was upregulated in mice undergoing UUO, MVs extracted from obstructed kidney tissues of mice and TGF-beta 1 -induced NRK-52E and NRK-49F cells. The overexpression of miRNA-153-3p remarkably induced apoptosis in tubular epithelial cells. Bcl-2 was verified to be the target gene of miRNA-153-3p, and the Bcl-2 level was negatively regulated by miRNA-153-3p. Overexpression of Bcl-2 reversed the effect of miRNA-153-3p on inducing cell apoptosis. CONCLUSIONS: MV-containing miRNA-153-3p released by tubulointerstitial fibroblasts transmits to the proximal tubular epithelial cells via the damaged tubule basement membrane. It induces the apoptosis of proximal tubular epithelial cells by inhibiting Bcl-2 level and further aggravates RIF.