Journal
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 220, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2021.112372
Keywords
Pulmonary fibrosis; Silicosis; Fibroblasts; TGFBR1; MiR-770-5p
Categories
Funding
- National Natural Science Foundation of China [82073518, 81874258]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD]
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This study found that miR-770-5p is downregulated in silica-induced pulmonary fibrosis and exerts an anti-fibrotic effect by targeting TGFBR1. Experimental evidence showed that miR-770-5p can reduce fibrotic lesions and control the activation of pulmonary fibroblasts.
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-beta 1-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 alpha-SMA in TGF-beta 1-treated MRC-5 cells. Transforming growth factor-beta receptor 1 (TGFBR1) was confirmed as a direct target of regulation by miR770-5p. The expression of TGFBR1 was significantly increased in pulmonary fibrosis. Knockdown of TGFBR1 blocked the transduction of the TGF-beta 1 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.
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