1. Exosomal miR-125a-5p regulates T lymphocyte subsets to promote silica-induced pulmonary fibrosis by targeting TRAF6.
- Author
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Ding M, Pei Y, Zhang C, Qi Y, Xia J, Hao C, and Yao W
- Subjects
- Animals, Mice, Cell Proliferation, T-Lymphocyte Subsets metabolism, T-Lymphocyte Subsets pathology, TNF Receptor-Associated Factor 6 genetics, TNF Receptor-Associated Factor 6 metabolism, MicroRNAs genetics, MicroRNAs metabolism, Pulmonary Fibrosis chemically induced, Pulmonary Fibrosis genetics, Pulmonary Fibrosis pathology, Silicon Dioxide toxicity, Silicosis genetics, Silicosis pathology, Exosomes genetics, Exosomes metabolism
- Abstract
Silicosis caused by long-term inhalation of crystalline silica during occupational activities seriously threatens the health of occupational populations. Imbalances in T helper 1(Th1), Th2, Th17, and regulatory T cells (Tregs) promote the development of pulmonary silicosis. Exosomes and their contents, especially microRNAs (miRNAs), represent a new type of intercellular signal transmission mediator related to various diseases including pulmonary fibrosis. However, whether exosomal miRNAs can affect the progression of silicosis by regulating T cell differentiation remains to be determined. To test this hypothesis, we established a miR-125a-5p antagomir mouse model and examined changes in miR-125a-5p levels and T cell subtypes. We found that miR-125a-5p levels were increased in lung tissues and serum exosomes in the silica group at 7 days and 28 days. Downregulation of miR-125a-5p attenuated α-smooth muscle actin (α-SMA), collagen I, fibronectin, p-p65, and p-inhibitor of nuclear factor kappa B (NF-κB) kinase (IKK) protein expression, while tumor necrosis factor receptor-associated factor 6 (TRAF6) and p-inhibitor of κBα (IKBα) expression were increased. MiR-125a-5p anta-miR treatment contributes to the maintenance of Th1/Th2 balance during the progression of pulmonary fibrosis. Our findings indicated that knockdown miR-125a-5p could regulate T lymphocyte subsets and significantly reduce pulmonary fibrosis by targeting TRAF6., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wu Yao reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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