Regulation of Collagen V Expression and Epithelial-Mesenchymal Transition by miR-185 and miR-186 during Idiopathic Pulmonary Fibrosis

Am J Pathol. 2016 Sep;186(9):2310-6. doi: 10.1016/j.ajpath.2016.04.015. Epub 2016 Jul 5.

Abstract

Idiopathic pulmonary fibrosis is a devastating disease, with no good diagnostic biomarker and limited treatment options. Previous studies suggest that collagen V overexpression and collagen V-mediated immune response play roles in the pathogenesis of idiopathic pulmonary fibrosis. This study aimed to identify dysregulated miRNA-related collagen V overexpression during idiopathic pulmonary fibrosis. We found that the expression levels of miR-185 and miR-186 were decreased in the lungs of idiopathic pulmonary fibrosis patients. The levels of miR-185 and miR-186 were not correlated with disease severity of idiopathic pulmonary fibrosis. The direct regulation of COL5A1 by miR-185 and miR-186 was confirmed by a luciferase reporter assay. Furthermore, mimics of miR-185 and miR-186 blocked transforming growth factor-β-induced collagen V overexpression and alleviated transforming growth factor-β-induced epithelial-mesenchymal transition in A549 cells and HCC827 cells. Our findings suggest that attenuated expression of miR-185 and miR-186 may be responsible for collagen V overexpression during idiopathic pulmonary fibrosis, and these miRNAs may serve as pathogenesis-related biomarkers and treatment targets.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Blotting, Western
  • Collagen Type V / biosynthesis*
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation / genetics
  • Humans
  • Idiopathic Pulmonary Fibrosis / genetics
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Real-Time Polymerase Chain Reaction

Substances

  • COL5A1 protein, human
  • Collagen Type V
  • MIRN185 microRNA, human
  • MIRN186 microRNA, human
  • MicroRNAs