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- Title
MiR-449a regulates autophagy to inhibit silica-induced pulmonary fibrosis through targeting Bcl2.
- Authors
Han, Ruhui; Ji, Xiaoming; Rong, Rong; Li, Yan; Yao, Wenxi; Yuan, Jiali; Wu, Qiuyun; Yang, Jingjin; Yan, Weiwen; Han, Lei; Zhu, Baoli; Ni, Chunhui
- 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:
- Subjects
SILICOSIS; LUNG diseases; PULMONARY fibrosis treatment; AUTOPHAGY; FIBROBLASTS; THERAPEUTICS
- Publication
Journal of Molecular Medicine, 2016, Vol 94, Issue 11, p1267
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-016-1441-0