Modulation of miRNA-10a-mediated TGF-β1/Smads signaling affects atrial fibrillation-induced cardiac fibrosis and cardiac fibroblast proliferation.

AF rat models and rat cardiac fibroblasts with overexpressed or inhibited miR-10a were used to investigate the possible role of miRNA-10a-mediated TGF-β1/Smads signaling in cardiac fibrosis and fibroblast proliferation in rats with atrial fibrillation (AF). Gene ontology and pathway enrichment analyses were used to identify the possible function of miR-10a in cardiac fibrosis. The results shown that overexpressed miR-10a significantly prolonged the duration of AF, further elevated the CVF, and increased the viability of cardiac fibroblasts in AF rats; these findings were in contrast to the findings for rats with inhibition of miR-10a (all P < 0.05). Moreover, miR-10a overexpression could promote miR-10a, collagen-I, collagen III, α-SMA, and TGF-β1 protein expression and increase the levels of hydroxyproline but reduced Smad7 protein expression in atrial tissues and cardiac fibroblasts in AF rats. Not surprisingly, inhibiting miR-10a led to completely contrasting results (all P < 0.05). Moreover, TGF-β1 treatment could reverse the inhibitory effect of miR-10a downregulation on cardiac fibrosis in cardiac fibroblasts. Bioinformatics analysis and luciferase reporter assay results demonstrated that miR-10a bound directly to the 3'-untranslated region of BCL6, which is involved in cell growth and proliferation. Thus, our study indicate that downregulation of miR-10a may inhibit collagen formation, reduce atrial structure remodeling, and decrease proliferation of cardiac fibroblasts, eventually suppressing cardiac fibrosis in AF rats via inhibition of the TGF-β1/Smads signaling pathway.