title: Regulation of Collagen V Expression and Epithelial-Mesenchymal Transition by miR-185 and miR-186 during Idiopathic Pulmonary Fibrosis.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Guang-Sheng
authors.initials: GS
authors.lastname: Lei
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Kline
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: University of Virginia School of Medicine, Charlottesville, Virginia.
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: chenzhan@iupui.edu.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000368:Aged; D015153:Blotting, Western; D024062:Collagen Type V / Q000096:biosynthesis*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C530725:COL5A1 protein, human; D024062:Collagen Type V; C552431:MIRN185 microRNA, human; C533096:MIRN186 microRNA, human; D035683:MicroRNAs