Open AccessmiR‐34a‐5p Attenuates EMT through targeting SMAD4 in silica‐induced pulmonary fibrosis
Author(s) -
Qi Yuanmeng,
Zhao Ahui,
Yang Peiyan,
Jin Luheng,
Hao Changfu
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15853
Subject(s) - silicosis , epithelial–mesenchymal transition , pulmonary fibrosis , vimentin , a549 cell , gene knockdown , cancer research , fibrosis , microrna , lung , medicine , chemistry , pathology , downregulation and upregulation , immunohistochemistry , gene , biochemistry
Abstract Silicosis is an incurable occupational disease, and its pathological feature is diffuse pulmonary fibrosis. Pulmonary epithelial‐mesenchymal transition (EMT) is one of the important events in the pathogenesis of silicosis. Previous studies found that abnormal expression of various microRNAs (miRNAs) involved in the development of lung fibrosis. However, their roles in silicosis have not been elucidated. To research the biological effects of miR‐34a in EMT process in silica‐induced lung fibrosis, we established the silicosis model in mouse and miR‐34a intervention in a cell model of TGF‐β1 stimulated lung epithelial cells (A549). The results showed that miR‐34a expression was down‐regulated in the fibrotic lung tissue after silica treatment, and it was similarly expressed in A549 cells stimulated by TGF‐β1. Meanwhile, silica‐induced EMT process can increase expression of two mesenchymal markers, α‐SMA and vimentin. Furthermore, overexpression miR‐34a markedly inhibited EMT stimulated by TGF‐β1. Mechanistically, SMAD4 was identified as the target of miR‐34a. SMAD4 levels decreased in mRNA and protein levels in A549 cells upon miR‐34a overexpression. In addition, the knockdown of SMAD4 blocked the EMT process. Taken together, miR‐34a regulated EMT, which might be partially realized by targeting SMAD4. Our data might provide new insight into treatment targets for silica‐induced pulmonary fibrosis.