miR-216a exacerbates TGF-β-induced myofibroblast transdifferentiation via PTEN/AKT signaling

Myofibroblast transdifferentiation is an important feature of cardiac fibrosis. Previous studies have indicated that microRNA-216a (miR-216a) is upregulated in response to transforming growth factor-β (TGF-β) in kidney cells and can activate Smad3; however, its role in myofibroblast transdifferentiation remains unclear. The present study aimed to investigate the role of miR-216a in TGF-β-induced myofibroblast transdifferentiation, and to determine the underlying mechanisms. Adult mouse cardiac fibroblasts were treated with TGF-β to induce myofibroblast transdifferentiation. An antagomir and agomir of miR-216a were used to inhibit or overexpress miR-216a in cardiac fibroblasts, respectively. Myofibroblast transdifferentiation was evaluated based on the levels of fibrotic markers and α-smooth muscle actin expression. The miR-216a antagomir attenuated, whereas the miR-216a agomir promoted TGF-β-induced myofibroblast transdifferentiation. Mechanistically, miR-216a accelerated myofibroblast transdifferentiation via the AKT/glycogen synthase kinase 3β signaling pathway, independent of the canonical Smad3 pathway. In addition, it was observed that miR-216a activated AKT via the downregulation of PTEN. In conclusion, miR-216a was involved in the regulation of TGF-β-induced myofibroblast transdifferentiation, suggesting that targeting miR-216a may aid in developing effective interventions for the treatment of cardiac fibrosis.