Suppressive effect of microRNA ‐29b on hepatic stellate cell activation and its crosstalk with TGF‐β1/Smad3

The microRNA (miR)‐29 family is closely associated with fibrotic processes by virtue of its low expression in many tissues during organ fibrosis. The present study investigated whether miR‐29b overexpression suppressed hepatic stellate cell (HSC) activation and its interactions with transforming growth factor (TGF)‐β1/mothers against decapentaplegic homolog 3 (Smad3), a classical signal transduction pathway contributing to the activation of HSCs. The results showed that transfection of LX‐2 (human HSC) cells with miR‐29b mimic or pSUPER‐Smad3 silencing (si)RNA resulted in significantly increased expression of miR‐29b and decreased expression of Smad3. miR‐29b overexpression inhibited proliferation of LX‐2 cells 24 h after transfection. Both miR‐29b overexpression and Smad3 silencing antagonized the effects of TGF‐β1 on the expression of α‐smooth muscle actin (α‐SMA) and collagen type I (col‐1). Furthermore, infection with miR‐29b mimics suppressed Smad3 and TGF‐β1 expression, suggesting that miR‐29b inhibited LX‐2 activation mediated by both Smad3 and TGF‐β1. Nevertheless, primary miR‐29a/b1, miR‐29b2/c and mature miR‐29b were downregulated by TGF‐β1 and stimulated by Smad3 silencing, suggesting that TGF‐β1/Smad3 signalling pathway regulate not just mature miR‐29b but also its transcription. In summary, our results show overwhelming evidence corroborating the suppressive effect of miR‐29b on TGF‐β1‐induced LX...
Source: Cell Biochemistry and Function - Category: Biochemistry Authors: Tags: Research Article Source Type: research