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

Developmental Biology
Yi LuDanrong Yang

Abstract

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)-β1 stimulation. We induced fibrogenic differentiation of LR-MSCs isolated from mice by TGF-β1. 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-β1 promoted fibrogenic differentiation of LR-MSCs and upregulated β-catenin and p-glycogen synthase kinase-3β, suggesting the activation of Wnt signaling. MicroRNA (MiR)-124-3p was significantly upregulated in TGF-β1 treated LR-MSCs compared to untreated cells. Intriguingly, silence of miR-124 reversed the TGF-β1-induced changes in cell viability and proliferation, and also led to a decrease of cell apoptosis. Additionally, in miR-124 silenced cells, α-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. ...Continue Reading

Citations

Apr 18, 2020·Journal of Experimental & Clinical Cancer Research : CR·Shiming TanQianjin Liao
May 14, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Stefanie Noel Sveiven, Tara M Nordgren
Aug 25, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardAfshin Taheriazam
Jun 16, 2021·American Journal of Respiratory Cell and Molecular Biology·Reiko SakuraiVirender K Rehan

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