miR-138 inhibits epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by regulating ZEB2.

Abstract

Silica dust is a common pollutant in the occupational environment, such as coal mines. Inhalation of silica dust can cause progressive pulmonary fibrosis and then silicosis. Silicosis is still one of the most harmful occupational diseases in the world, so the study of its pathogenesis is necessary for the treatment of silicosis. In this study, we constructed a mouse model of pulmonary fibrosis via intratracheal instillation of silica particles and identified the decreased expression of miR-138 in fibrotic lung tissues of mice. Moreover, the overexpression of miR-138 retarded the process of epithelial-mesenchymal transition (EMT) in a mouse model of silica particles exposure and epithelial cells stimulated by silica particles. Further studies showed that ZEB2 was one of the potential targets of miR-138, and the up-regulation of miR-138 reduced ZEB2 levels in mouse lung tissues and in epithelial cells. We next found that the expression levels of ɑ-SMA and Vimentin were significantly increased and E-cadherin levels were decreased after transfection with miR-138 inhibitor in epithelial cells. However, these effects were abated by the knockdown of ZEB2. Consistently, the increased migration ability of epithelial cells by miR-138 inhibitor transfection was also reversed by the knockdown of ZEB2. Collectively, we revealed that miR-138 significantly targeted ZEB2, thus inhibited the EMT process and mitigated the development of pulmonary fibrosis. miR-138 may be a potential target for the treatment of pulmonary fibrosis.

• Authors: Qiuyun Wu, Wenwen Gui, Biyang Jiao, Lei Han, Feng Wang
• Journal: Toxicology (Toxicology) Vol. 461 Pg. 152925 (09 2021) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 34481903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Environmental Pollutants
• MIRN138 microRNA, mouse
• MicroRNAs
• ZEB2 protein, mouse
• Zinc Finger E-box Binding Homeobox 2
• Silicon Dioxide

Topics

• A549 Cells
• Animals
• Cell Movement (genetics)
• Disease Models, Animal
• Environmental Pollutants (administration & dosage, toxicity)
• Epithelial Cells (drug effects, metabolism)
• Epithelial-Mesenchymal Transition (drug effects)
• Fibrosis (pathology)
• Gene Knockdown Techniques
• Humans
• Inhalation Exposure (adverse effects)
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Pulmonary Fibrosis (chemically induced, genetics, physiopathology)
• Silicon Dioxide (administration & dosage, toxicity)
• Silicosis (physiopathology)
• Zinc Finger E-box Binding Homeobox 2 (genetics, metabolism)