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- Title
miR-29 inhibits bleomycin-induced pulmonary fibrosis in mice.
- Authors
Xiao, Jun; Meng, Xiao-Ming; Huang, Xiao R; Chung, Arthur Ck; Feng, Yu-Lin; Hui, David Sc; Yu, Cheuk-Man; Sung, Joseph Jy; Lan, Hui Y
- Abstract
Loss of microRNA-29 (miR-29) is known to be a mechanism of transforming growth factor-β (TGF-β)-mediated pulmonary fibrosis, but the therapeutic implication of miR-29 for pulmonary fibrosis remains unexplored. The present study investigated whether miR-29 had therapeutic potential for lung disease induced by bleomycin in mice. In addition, the signaling mechanisms that regulated miR-29 expression were investigated in vivo and in vitro. We found that miR-29 was a downstream target gene of Smad3 and negatively regulated by TGF-β/Smad signaling in fibrosis. This was evidenced by the findings that mice or pulmonary fibroblasts null for Smad3 were protected against bleomycin or TGF-β1-induced loss of miR-29 along with fibrosis in vivo and in vitro. Interestingly, overexpression of miR-29 could in turn negatively regulated TGF-β and connective tissue growth factor (CTGF) expression and Smad3 signaling. Therefore, Sleeping Beauty (SB)-mediated miR-29 gene transfer into normal and diseased lung tissues was capable of preventing and treating pulmonary fibrosis including inflammatory macrophage infiltration induced by bleomycin in mice. In conclusion, miR-29 is negatively regulated by TGF-β/Smad3 and has a therapeutic potential for pulmonary fibrosis. SB-mediated miR-29 gene therapy is a non-invasive therapeutic strategy for lung disease associated with fibrosis.
- Publication
Molecular therapy : the journal of the American Society of Gene Therapy, 2012, Vol 20, Issue 6, p1251
- ISSN
1525-0024
- Publication type
Journal Article
- DOI
10.1038/mt.2012.36