The miR-130a-3p/TGF-βRII Axis Participates in Inhibiting the Differentiation of Fibroblasts Induced by TGF-β1

Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease that has a poor prognosis. Abnormal activation of transforming growth factor-beta 1 (TGF-beta 1) plays a crucial role in fibroblast differentiation. Mesenchymal stem cells (MSCs) are currently being considered for the treatment of PF, but the regulatory mechanisms are poorly understood. We co-cultured bone marrow-derived MSCs and mouse lung fibroblasts (MLg) in the presence of TGF-beta 1, and studied the protein/mRNA expression of fibrosis markers and related signaling pathways. The effects of miR-130a-3p and TGF-beta receptor II (TGF-beta RII) on the differentiation of MLg induced by TGF-beta 1 were studied using immunofluorescence assay, Western blot, and quantitative real-time PCR techniques, respectively. Our results showed that MSCs reversed the overexpression of fibrosis markers and TGF-beta 1/Smad signaling pathway proteins and mRNAs after TGF-beta 1 treatment and increased the level of miR-130a-3p. TGF-beta RII was identified as a target of miR-130a-3p and was evaluated by dual-luciferase reporter assay. The miR-130a-3p/TGF-beta RII axis could suppress the differentiation of lung fibroblasts via the TGF-beta 1/Smad signaling pathway, thereby reducing the process of PF.

Automated summary

The study demonstrated that MSCs reversed the overexpression of fibrosis markers and TGF-beta 1/Smad signaling pathway proteins and mRNAs after TGF-beta 1 treatment and increased the level of miR-130a-3p. The miR-130a-3p/TGF-beta RII axis could suppress the differentiation of lung fibroblasts via the TGF-beta 1/Smad signaling pathway, thereby reducing the process of PF.