title: Participation of miR-200 in pulmonary fibrosis.
abstract: Excessive extracellular matrix production by fibroblasts in response to tissue injury contributes to fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF). Epithelial-mesenchymal transition, involving transition of alveolar epithelial cells (AECs) to pulmonary fibroblasts, appears to be an important contributory process to lung fibrosis. Although aberrant expression of microRNAs (miRs) is involved in a variety of pathophysiologic processes, the role of miRs in fibrotic lung diseases is less well understood. In the present study, we found that miR-200a, miR-200b, and miR-200c are significantly down-regulated in the lungs of mice with experimental lung fibrosis. Levels of miR-200a and miR-200c were reduced in the lungs of patients with IPF. miR-200 had greater expression in AECs than in lung fibroblasts, and AECs from mice with experimental pulmonary fibrosis had diminished expression of miR-200. We found that the miR-200 family members inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition of AECs. miR-200 family members can reverse the fibrogenic activity of pulmonary fibroblasts from mice with experimental pulmonary fibrosis and from patients with IPF. Indeed, the introduction of miR-200c diminishes experimental pulmonary fibrosis in mice. Thus, the miR-200 family members participate importantly in fibrotic lung diseases and suggest that restoring miR-200 expression in the lungs may represent a novel therapeutic approach in treating pulmonary fibrotic diseases.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Shanzhong
authors.initials: S
authors.lastname: Yang
authors.forename: Sami
authors.initials: S
authors.lastname: Banerjee
authors.forename: Andressa
authors.initials: A
authors.lastname: de Freitas
authors.forename: Yan Y
authors.initials: YY
authors.lastname: Sanders
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D008168:Lung / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D016212:Transforming Growth Factor beta