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

Abstract

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.