MiR-124 regulates transforming growth factor-β1 induced differentiation of lung resident mesenchymal stem cells to myofibroblast by repressing Wnt/β-catenin signaling

Lung resident mesenchymal stem cells (LR-MSCs) contribute to the progression of idiopathic pulmonary fibrosis (IPF). We aimed to investigate the molecular mechanism underlying LR-MSCs regulation upon transforming growth factor (TGF)-beta 1 stimulation. We induced fibrogenic differentiation of LR-MSCs isolated from mice by TGF-beta 1. Several stem cell markers were detected by flow cytometric analysis. Protein expression level was tested by Western blotting and mRNA level was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, proliferation and apoptosis were measured. TGF-beta 1 promoted fibrogenic differentiation of LR-MSCs and upregulated beta-catenin and p-glycogen synthase kinase-3 beta, suggesting the activation of Wnt signaling. MicroRNA (MiR)-124-3p was significantly upregulated in TGF-beta 1 treated LR-MSCs compared to untreated cells. Intriguingly, silence of miR-124 reversed the TGF-beta 1-induced changes in cell viability and proliferation, and also led to a decrease of cell apoptosis. Additionally, in miR-124 silenced cells, alpha-smooth muscle actin, collagen I and fibronectin were downregulated compared to control cells. We ultimately identified a new target of miR-124, AXIN1, which was repressed by miR-124. In conclusion, miR-124 regulates AXIN1 to activate Wnt signaling and therefore plays a crucial role in the TGF-beta 1-induced fibrogenic differentiation.