miR-18a-5p Inhibits Sub-pleural Pulmonary Fibrosis by Targeting TGF-β Receptor II

Qian Zhang, Hong Ye, Fei Xiang, Lin Jie Song, Li Ling Zhou, Peng Cheng Cai, Jian Chu Zhang, Fan Yu, Huan Zhong Shi, Yunchao Su, Jian Bao Xin, Wan Li Ma

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease that typically leads to respiratory failure and death within 3–5 years of diagnosis. Sub-pleural pulmonary fibrosis is a pathological hallmark of IPF. Bleomycin treatment of mice is a an established pulmonary fibrosis model. We recently showed that bleomycin-induced epithelial-mesenchymal transition (EMT) contributes to pleural mesothelial cell (PMC) migration and sub-pleural pulmonary fibrosis. MicroRNA (miRNA) expression has recently been implicated in the pathogenesis of IPF. However, changes in miRNA expression in PMCs and sub-pleural fibrosis have not been reported. Using cultured PMCs and a pulmonary fibrosis animal model, we found that miR-18a-5p was reduced in PMCs treated with bleomycin and that downregulation of miR-18a-5p contributed to EMT of PMCs. Furthermore, we determined that miR-18a-5p binds to the 3′ UTR region of transforming growth factor β receptor II (TGF-βRII) mRNA, and this is associated with reduced TGF-βRII expression and suppression of TGF-β-Smad2/3 signaling. Overexpression of miR-18a-5p prevented bleomycin-induced EMT of PMC and inhibited bleomycin-induced sub-pleural fibrosis in mice. Taken together, our data indicate that downregulated miR-18a-5p mediates sub-pleural pulmonary fibrosis through upregulation of its target, TGF-βRII, and that overexpression of miR-18a-5p might therefore provide a novel approach to the treatment of IPF.

Original languageEnglish (US)
Pages (from-to)728-738
Number of pages11
JournalMolecular Therapy
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2017

Keywords

  • TGF-β1
  • epithelial-mesenchymal transition
  • fibrosis
  • miR-18a
  • pleural mesothelial cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Zhang, Q., Ye, H., Xiang, F., Song, L. J., Zhou, L. L., Cai, P. C., Zhang, J. C., Yu, F., Shi, H. Z., Su, Y., Xin, J. B., & Ma, W. L. (2017). miR-18a-5p Inhibits Sub-pleural Pulmonary Fibrosis by Targeting TGF-β Receptor II. Molecular Therapy, 25(3), 728-738. https://doi.org/10.1016/j.ymthe.2016.12.017