miR-29 inhibits bleomycin-induced pulmonary fibrosis in mice

Mol Ther. 2012 Jun;20(6):1251-60. doi: 10.1038/mt.2012.36. Epub 2012 Mar 6.


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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin
  • Cells, Cultured
  • DNA Transposable Elements
  • Disease Models, Animal
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression
  • Gene Expression Regulation / drug effects
  • Gene Transfer Techniques
  • Genetic Therapy
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / administration & dosage
  • MicroRNAs / metabolism*
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / genetics*
  • Pulmonary Fibrosis / prevention & control*
  • Signal Transduction
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology


  • DNA Transposable Elements
  • MIRN29 microRNA, mouse
  • MicroRNAs
  • Smad3 Protein
  • Transforming Growth Factor beta
  • Bleomycin