MicroRNA-29b inhibits TGF-β1-induced fibrosis via regulation of the TGF-β1/Smad pathway in primary human endometrial stromal cells

Abstract

Transforming growth factor (TGF)-β1 has a key role in the regulation of fibrosis and organ dysfunction. During the pathogenesis and progression of vital organ fibrosis, the microRNA (MIR)-29 family is irregularly downregulated and exogenous supplementation of MIR-29b has a strong anti-fibrotic capacity. However, whether TGF-β1 is able to provoke endometrial fibrosis, and the role of MIR-29 in endometrial fibrosis remain unclear. In the present study, RT-qPCR, immunocytochemistry, western blot analysis, scanning electron microscopy, immunofluorescence staining, cell proliferation assay and flow cytometric analysis were employed. The results demonstrated that the expression levels of collagen, type 1, alpha 1 (COL1A1), α-smooth muscle actin (α-SMA) and phosphorylated (p)-Smad2/3 were increased, whereas MIR-29b and maternally expressed gene 3 (MEG3) were decreased in primary endometrial stromal cells (ESCs) in response to TGF-β1 stimulation, in a time and dose-dependent manner. Furthermore, overexpression of MIR-29b markedly reduced the expression levels of COL1A1 and α-SMA, and decreased the expression and nuclear accumulation of p-Smad2/3. In addition, ectopic overexpression of MIR-29b increased the expression levels of MEG3, inhibited myofibroblast-like cell proliferation and induced apoptosis. These findings indicated that MIR-29b may have a significant anti-fibrotic role, and may attenuate TGF-β1-induced fibrosis in ESCs. Therefore, exogenous MIR-29b may serve as a potential therapeutic agent for the treatment of endometrial fibrosis.