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Aberrant expression of miR-125a-3p promotes fibroblast activation via Fyn/STAT3 pathway during silica-induced pulmonary fibrosis.
- Source :
-
Toxicology . Feb2019, Vol. 414, p57-67. 11p. - Publication Year :
- 2019
-
Abstract
- Highlights • Post-translational of epigenetic plays a key role in lung fibroblast activation and silica-induced fibrosis. • MiR-125a-3p regulates lung fibroblast activation and silica-induced fibrosis by targeting Fyn. • MiR-125a-3p/Fyn/STAT3signaling pathway is a potential therapeutic approach for pulmonary fibrosis. Abstract Various miRNAs are dysregulated during initiation and progression of pulmonary fibrosis. However, their function remains limited in silicosis. Here, we observed that miR-125a-3p was downregulated in silica-induced fibrotic murine lung tissues. Ectopic miR-125a-3p expression with chemotherapy attenuated silica-induced pulmonary fibrosis. Further in vitro experiments revealed that TGF-β1 effectively decreased miR-125a-3p expression in fibroblast lines (NIH/3T3 and MRC-5). Overexpression of miR-125a-3p blocked fibroblast activation stimulated by TGF-β1. Mechanistically, miR-125a-3p could bind to the 3′-untranslated region of Fyn and inhibit its expression in both mRNA and protein levels, thus causing inactivation of Fyn downstream effector STAT3. Fyn and p-STAT3, as opposed to miR-125a-3p expression, were elevated in silica-induced fibrotic murine lung tissues and TGF-β1-treated fibroblast lines. Furthermore, Fyn knockdown or p-STAT3 suppression effectively attenuated fibroblast activation and ECM production. Taken together, miR-125a-3p is involved in fibrosis pathogenesis by fibroblast activation, suggesting that targeting miR-125a-3p/Fyn/STAT3 signaling pathway could be a potential therapeutic approach for pulmonary fibrosis. [ABSTRACT FROM AUTHOR]
- Subjects :
- *MICRORNA
*FIBROBLASTS
*PULMONARY fibrosis
*DISEASE progression
*CANCER chemotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 0300483X
- Volume :
- 414
- Database :
- Academic Search Index
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 134379036
- Full Text :
- https://doi.org/10.1016/j.tox.2019.01.007