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.

Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture

“…10 Recently, studies have shown that various microRNAs (miRNAs), predominantly the miR-200 family, have an important role in both EMT and lung fibrosis. 11,12 The miR-200 family member miR-200c is believed to be pivotal when it comes to the downregulation of E-cadherin, one of the hallmarks of EMT. 13 When this miRNA is downregulated, its target, the transcription factor ZEB1, is free to downregulate E-cadherin expression.…”

MicroRNA Regulation of Nonmuscle Myosin Light Chain Kinase Expression in Human Lung Endothelium

“…In addition, miRNAs recently emerged as novel biomarkers and therapeutic strategies because miRNA deregulation is associated with diverse disorders such as cancer, neurodegenerative disease, and cardiovascular and myeloproliferative diseases (reviewed in Refs. 18 and 19) as well as with complex inflammatory lung diseases such as ALI, asthma, pulmonary arterial hypertension, lung cancer, and idiopathic pulmonary fibrosis (20)(21)(22)(23)(24). Because the role of miRNAs in posttranscriptional MYLK gene regulation and in the pathogenesis of ALI has not been investigated, we used a MYLK 39UTR luciferase reporter, combined with overexpression of mature miRNAs and endogenous …”

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

“…Alterations in these miRNAs have also been demonstrated in lung fibroblasts or alveolar epithelial cells from IPF patients and pulmonary fibrosis animal models. 17,18,[21][22][23][24] However, changes in miRNAs in PMCs and their roles in PMC EMT and sub-pleural fibrosis have not been described. In the present study, we used cultured PMCs and a mouse pulmonary fibrosis animal model to explore the role of miRNA in PMC EMT and sub-pleural pulmonary fibrosis.…”