AUTHOR=Liao Weitang , Liang Peifen , Liu Bo , Xu Zhenjian , Zhang Lili , Feng Min , Tang Ying , Xu Anping 

TITLE=MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

JOURNAL=Frontiers in Physiology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.01093

DOI=10.3389/fphys.2020.01093

ISSN=1664-042X

ABSTRACT=Renal fibrosis is usually the final outcome of a wide variety of kidney diseases. Researches report that microRNAs (miRNAs) play a mediatory role in the pathogenesis of fibrosis. However, the role and underlying mechanisms of microRNAs in renal fibrosis are complicated and largely unclear. Here, we find that miR-140-5p is down-regulated in unilateral ureteral obstruction (UUO) mice and human proximal tubule epithelial cells (HK-2) stimulated with transforming growth factor beta 1 (TGF-β1). Knockdown of miR-140-5p upregulate the expression of collagen I, collagen IV and α-SMA, decrease the expression of E-cadherin, increase the phosphorylation of Smad-2/3. In contrast, overexpression of miR-140-5p decrease the expression of collagen I, collagen IV and α-SMA, enhance the expression of E-cadherin, inhibites the phosphorylation of Smad-2/3 in HK2 cells treated with TGF-β1. Luciferase assay revealed that miR-140-5p directly targets at the 3’UTR of TGFBR1 with the results showing that overexpression of miR-140-5p significantly decreased the expression of TGFBR1 in HK2 cells. Furthermore, knockdown of TGFBR1 has the similar effect of miR-140-5p inhibition on TGF-β1/smad signal pathway activation. In contrast, overexpression of TGFBR1 reverse the effect of miR-140-5p inhibition on the activation of TGF-β1/smad signal pathway. Therefore, our findings indicated that miR-140-5p may attenuates renal fibrosis by suppressing TGF-β1/smad signaling path way activation partially via targeting TGFBR1 and represents a novel and promising therapeutic target for renal fibrotic.