Lack of microRNA‐155 ameliorates renal fibrosis by targeting PDE3A/TGF‐β1/Smad signaling in mice with obstructive nephropathy.

Although microRNA‐155 (miR‐155) is implicated in the pathogenesis of several fibrotic diseases, information regarding its functional role in renal fibrosis is limited. The current study aims to investigate the effects of miR‐155 on renal fibrosis in unilateral ureteral occlusion (UUO) mice. MiR‐155 level was significantly increased in renal tissues of UUO mice and TGF‐β1‐treated HK2 cells. Masson's trichrome staining showed that delivery of adeno‐associated virus encoding miR‐155 inhibitor led to a decrease in renal fibrosis induced by UUO. The increased expression of plasminogen activator inhibitor type 1, collagen III and collagen IV was also inhibited after miR‐155 inhibition. In addition, miR‐155 knockdown also prevented TGF‐β1‐induced epithelial–mesenchymal transition, concomitantly with a restoration of E‐cadherin expression and a decrease of vimentin expression. Computational analysis revealed that miR‐155 directly targets at 3′UTR of PDE3A. Overexpression of miR‐155 suppressed the luciferase activity and protein expression of PDE3A, whereas inhibition of miR‐155 increased PDE3A luciferase activity and expression. Furthermore, miR‐155 inhibited TGF‐β1‐induced the increase of TGF‐β1 expression and Smad‐2/3 phosphorylation in HK2 cells. In contrast, knockdown of PDE3A reversed the effect of miR‐155 inhibition on TGF‐β1 expression. This study demonstrates that knockdown of miR‐155 attenuates renal fibrosis via inhibiting TGF‐β1/Smad signaling activation by targeting the upstream molecule PDE3A. This study suggests that miR‐155 inhibition may be a novel therapeutic approach for preventing fibrotic kidney diseases. [ABSTRACT FROM AUTHOR]