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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

Affiliations ¹ Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. ² The second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, China. ³ Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. ⁴ UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia.

刊名

Environmental toxicology

年份

2022

卷号

Vol.37 No.8

页码

2019-2032

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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