Microvesicles containing miR-34a induce apoptosis of proximal tubular epithelial cells and participate in renal interstitial fibrosis

Exp Ther Med. 2019 Mar;17(3):2310-2316. doi: 10.3892/etm.2019.7197. Epub 2019 Jan 24.

Abstract

Function and potential mechanism of microvesicles (MVs) containing microRNA34a in renal interstitial fibrosis were investigated. A rat model of renal interstitial fibrosis was established by unilateral ureteral ligation (UUO). Rat proximal tubular epithelial cell line (NRK-52E) was used to explore the effect of MVs containing microRNA-34a on tubular epithelial cells during fibrosis, which were secreted by tubulointerstitial fibroblasts. Regardless of the UUO renal interstitial fibrosis model, or the TGF-β1-treated renal tubular epithelial cells, microRNA-34a was increased in the MVs secreted by tubulointerstitial fibroblasts. miR-34a could be transmitted through the damaged tubule basement membrane to proximal tubular epithelial cells, where it induced apoptosis of renal tubular epithelial cells by inhibiting the expression of Bcl-2, further aggravating renal interstitial fibrosis. MicroRNA-34a secreted by damaged renal interstitial fibroblasts can promote renal tubular epithelial cell apoptosis and participate in renal interstitial fibrosis by inhibiting Bcl-2.

Keywords: Bcl-2; apoptosis; fibrosis; miR-34a.