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作者

Xinru Pang, Haojun Shi, Xiaoshu Chen, Chao Li, Bin Shi, Abrey J Yeo, Martin F Lavin, Qiang Jia, Hua Shao, Juan Zhang, Gongchang Yu

作者单位

UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia. The second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, China. Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. Affiliations Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

刊名

Environmental toxicology

年份

2022

ISSN

1522-7278

关键词

Fos-related antigen 1 epithelial-mesenchymal transformation miRNA-34c-5p pulmonary fibrosis silica.

摘要

Silica dust particles are representative of air pollution and long-term inhalation of silicon-containing dust through the respiratory tract can cause pulmonary fibrosis. Epithelial-mesenchymal transformation plays an important role in the development of fibrosis. This process can relax cell-cell adhesion complexes and enhance cell migration and invasion properties of these cells. Dysregulation of microRNA-34c is highly correlated with organ fibrosis including pulmonary fibrosis. In this study,...更多

Silica dust particles are representative of air pollution and long-term inhalation of silicon-containing dust through the respiratory tract can cause pulmonary fibrosis. Epithelial-mesenchymal transformation plays an important role in the development of fibrosis. This process can relax cell-cell adhesion complexes and enhance cell migration and invasion properties of these cells. Dysregulation of microRNA-34c is highly correlated with organ fibrosis including pulmonary fibrosis. In this study, we found that miR-34c-5p could alleviate the occurrence and development of silica-mediated EMT. Fos-related antigen 1 was identified as a functional target of miR-34c-5p by bioinformatics analysis and the dual luciferase gene reporting assay. Importantly, chemically induced up-regulation of hsa-miR-34c-5p correlated inversely with the expression of Fra-1 and further exploration found that the miR-34c-5p/Fra-1 axis inhibits the activation of the phosphatase and tensin homolog deleted on chromosome 10/phosphatidylinositol-4,5-bisphosphate3-kinase/protein kinase B signaling pathway. In addition, through interaction with PTEN/p53 it inhibits the proliferation and migration of human bronchial epithelial cells stimulated by silica, and promotes cell apoptosis, thereby preventing EMT. This finding provides a promising biomarker for the diagnosis and prognosis of pulmonary fibrosis. Furthermore, overexpression of miR-34c-5p represents a potential therapeutic approach.收起

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