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MiR-449a regulates autophagy to inhibit silica-induced pulmonary fibrosis through targeting Bcl2.
- Source :
-
Journal of Molecular Medicine . Nov2016, Vol. 94 Issue 11, p1267-1279. 13p. - Publication Year :
- 2016
-
Abstract
- Silicosis is a fatal pulmonary fibrotic disorder characterized by accumulation of fibroblasts and myofibroblasts and deposition of extracellular matrix proteins. MiR-449a is a potential mediator of many cellular processes, including cell proliferation, differentiation, and apoptosis. We hypothesized that miR-449a may play a crucial role in the progression of pulmonary fibrogenesis. Here, we described miR-449a as a new autophagy-regulated miRNA. Importantly, miR-449a expression was significantly decreased in lung tissues of mice with silica treatment, and it was similarly expressed in NIH-3T3 and MRC-5 cells stimulated with TGF-β1. The activity of autophagy was inhibited in fibrotic lung tissues and TGF-β1-treated fibroblasts. To investigate the potential effect of miR-449a, we overexpressed miR-449a in mouse models and found that miR-449a significantly reduced both the distribution and severity of lung lesions induced by silica. In addition, miR-449a was observed to induce the activity of autophagy in vivo and in vitro. Notably, Bcl2 was identified as a target of miR-449a. Bcl2 levels were decreased in NIH-3T3 cells upon miR-449a overexpression. Indeed, the Bcl2 3′ UTR contained functional miR-449a responsive sequences. Furthermore, TGF-β1 was observed to increase the expression of Bcl2 via the MAPK/ERK pathway. These results suggest that miR-449a is an important regulator of autophagy, as well as a novel endogenous suppressor of pulmonary fibrosis. Key message: [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09462716
- Volume :
- 94
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 118887588
- Full Text :
- https://doi.org/10.1007/s00109-016-1441-0