miR-770-5p inhibits the activation of pulmonary fibroblasts and silica-induced pulmonary fibrosis through targeting TGFBR1.

Silicosis is a devastating interstitial lung disease arising from long-term exposure to inhalable silica. Regrettably, no therapy currently can effectively reverse the silica-induced fibrotic lesion. Emerging evidence has indicated that the dysregulation of microRNAs is involved in silica-induced pulmonary fibrosis. The aim of this study is to explore the expression pattern and underlying mechanisms of miR-770-5p in silica-induced pulmonary fibrosis. Consistent with our previous miRNA microarray analysis, the results of qRT-PCR showed that miR-770-5p expression was downregulated in silica-induced pulmonary fibrosis in humans and animal models. Administration of miR-770-5p agomir significantly reduced the fibrotic lesions in the lungs of mice exposed to silica dust. MiR-770-5p also exhibited a dramatic reduction in TGF-β1-activated human pulmonary fibroblasts (MRC-5). Transfection of miR-770-5p mimics significantly decreased the viability, migration ability, and S/G0 phase distribution, as well as the expression of fibronectin, collagen I, and α-SMA in TGF-β1-treated MRC-5 cells. Transforming growth factor-β receptor 1 (TGFBR1) was confirmed as a direct target of regulation by miR-770-5p. The expression of TGFBR1 was significantly increased in pulmonary fibrosis. Knockdown of TGFBR1 blocked the transduction of the TGF-β1 signaling pathway and attenuated the activation of MRC-5 cells, while overexpression of TGFBR1 effectively restored the activation of MRC-5 cells inhibited by miR-770-5p. Together, our results demonstrated that miR-770-5p exerted an anti-fibrotic effect in silica-induced pulmonary fibrosis by targeting TGFBR1. Targeting miR-770-5p might provide a new therapeutic strategy to prevent the abnormal activation of pulmonary fibroblasts in silicosis.

Yuan J ，Li P ，Pan H ，Xu Q ，Xu T ，Li Y ，Wei D ，Mo Y ，Zhang Q ，Chen J ，Ni C ... -  《-》

miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin α6 in Silica-Induced Pulmonary Fibrosis.

Yuan J ，Li P ，Pan H ，Li Y ，Xu Q ，Xu T ，Ji X ，Liu Y ，Yao W ，Han L ，Ni C ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1.

Wu Q ，Xu T ，Liu Y ，Li Y ，Yuan J ，Yao W ，Xu Q ，Yan W ，Ni C ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Long noncoding RNA-SNHG20 promotes silica-induced pulmonary fibrosis by miR-490-3p/TGFBR1 axis.

Silicosis is a universal occupational disease, which is caused by long-term crystalline silica exposure. Recent studies have shown that noncoding RNAs participate in diverse pathological cellular pathways. However, the precise regulation mechanism remains limited in silicosis. Here, we established a silica-induced mouse fibrosis model (all mice received a one-time intratracheal instillation with 50 mg/kg of silica in 0.05 mL sterile saline). MiR-490-3p was significantly downregulated in silica-induced fibrotic mouse lung tissues and TGF-β1 treated fibroblasts. Moreover, overexpressed miR-490-3p could relieve silica-induced lung fibrosis in vivo, and prevent the process of fibroblast-to-myofibroblast transition(FMT)in vitro. Mechanistically, TGFBR1 was one of the major target genes of miR-490-3p, and tightly associated with the process of fibroblasts activation. SNHG20, as opposed to miR-490-3p expression, was elevated in TGF-β1-treated fibroblast cell lines and contributed to decreased levels of miR-490-3p. Taken together, these data indicated that miR-490-3p plays a key role in silica-induced pulmonary fibrosis. Our results suggested that SNHG20/miR-490-3p/TGFBR1 axis may provide a new treatment target of pulmonary fibrosis.

Cheng D ，Xu Q ，Liu Y ，Li G ，Sun W ，Ma D ，Ni C ... -  《-》

MiR-449a regulates autophagy to inhibit silica-induced pulmonary fibrosis through targeting Bcl2.

Han R ，Ji X ，Rong R ，Li Y ，Yao W ，Yuan J ，Wu Q ，Yang J ，Yan W ，Han L ，Zhu B ，Ni C ... -  《-》