MiR-150-5p Alleviates Renal Tubule Epithelial Cell Fibrosis via the Inhibition of Epithelial-Mesenchymal Transition by Targeting ZEB1

Abstract

Introduction: Although microRNA (miR)-150-5p participates in the progression of renal fibrosis, its mechanism of action remains elusive. Methods: A mouse model of unilateral ureteral obstruction was used. The in vitro renal fibrosis model was established by stimulating human kidney 2 (HK-2) cells with transforming growth factor beta 1 (TGF-β1). The expression profiles of miR-150-5p, zinc finger E-box binding homeobox 1 (ZEB1), and other fibrosis- and epithelial-mesenchymal transition (EMT)-linked proteins were determined using Western blot and quantitative reverse transcription polymerase chain reaction. The relationship between miR-150-5p and ZEB1 in HK-2 cells was confirmed by a dual-luciferase reporter assay. Results: Both in vivo and in vitro renal fibrosis models revealed reduced miR-150-5p expression and elevated ZEB1 level. A significant decrease in E-cadherin levels, as well as increases in alpha smooth muscle actin (α-SMA) and collagen type I (Col-I) levels, was seen in TGF-β1-treated HK-2 cells. The overexpression of miR-150-5p ameliorated TGF-β1-mediated fibrosis and EMT. Notably, miR-150-5p acts by directly targeting ZEB1. A significant reversal of the inhibitory impact of miR-150-5p on TGF-β1-mediated fibrosis and EMT in HK-2 cells was observed upon ZEB1 overexpression. Conclusion: MiR-150-5p suppresses TGF-β1-induced fibrosis and EMT by targeting ZEB1 in HK-2 cells, providing helpful insights into the therapeutic intervention of renal fibrosis.