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

Abstract

<b><i>Introduction:</i></b> Although microRNA (miR)-150-5p participates in the progression of renal fibrosis, its mechanism of action remains elusive. <b><i>Methods:</i></b> 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 (<i>ZEB1</i>), 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 <i>ZEB1</i> in HK-2 cells was confirmed by a dual-luciferase reporter assay. <b><i>Results:</i></b> Both in vivo and in vitro renal fibrosis models revealed reduced miR-150-5p expression and elevated ZEB<i>1</i> 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 <i>ZEB1</i>. 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 <i>ZEB1</i> overexpression. <b><i>Conclusion:</i></b> MiR-150-5p suppresses TGF-β1-induced fibrosis and EMT by targeting <i>ZEB1</i> in HK-2 cells, providing helpful insights into the therapeutic intervention of renal fibrosis.