Integrated analyses identify the involvement of microRNA-26a in epithelial–mesenchymal transition during idiopathic pulmonary fibrosis

Abstract

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and highly lethal fibrotic lung disease with poor treatment and unknown etiology. Emerging evidence suggests that epithelial–mesenchymal transition (EMT) has an important role in repair and scar formation following epithelial injury during pulmonary fibrosis. Although some miRNAs have been shown to be dysregulated in the pathophysiological processes of IPF, limited studies have payed attention on the participation of miRNAs in EMT in lung fibrosis. In our study, we identified and constructed a regulation network of differentially expressed IPF miRNAs and EMT genes. Additionally, we found the downregulation of miR-26a in mice with experimental pulmonary fibrosis. Further studies showed that miR-26a regulated HMGA2, which is a key factor in the process of EMT and had the maximum number of regulating miRNAs in the regulation network. More importantly, inhibition of miR-26a resulted in lung epithelial cells transforming into myofibroblasts in vitro and in vivo, whereas forced expression of miR-26a alleviated TGF-β1- and BLM-induced EMT in A549 cells and in mice, respectively. Taken together, our study deciphered the essential role of miR-26a in the pathogenesis of EMT in pulmonary fibrosis, and suggests that miR-26a may be a potential therapeutic target for IPF.

rs2910164 Polymorphism Confers a Decreased Risk for Pulmonary Hypertension by Compromising the Processing of microRNA-146a

“…Variants in miRNAs have been reported to be correlated with a number of human diseases [22,23,24]. As shown by Jazdzewski et al, a C allele rs2910164 polymorphism significantly compromises the processing and maturing of miRNA and results in an approximately 2-fold decrease in production of mature miR-146a than a G allele in a thyroid cell line [25].…”

Tanshinone IIA ameliorates bleomycin-induced pulmonary fibrosis and inhibits transforming growth factor-beta-β–dependent epithelial to mesenchymal transition

“…Tanjore et al [7] have demonstrated that EMT of alveolar epithelial cells contributes to fibroblasts in bleomycin (BLM)einduced lung fibrosis. It has been suggested that suppression of abnormal EMT process either with exogenous reagents such as methacycline and sorafenib [8,9] or endogenous regulators such as microRNA-26a and microRNA-21 [10,11] can ameliorate pulmonary fibrogenesis. These previous studies support a concept that EMT signaling is important to lung fibrosis, and inhibition of EMT may represent a useful approach to attenuate pulmonary fibrosis.…”

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

“…Approximately 10% of miRNAs expressed in the lungs of IPF patients show significant deregulation. 17 It has been found that miRNA-326, 18 let-7d, miRNA-29, miRNA-18a, 17 miRNA-26a, [18][19][20] and miRNA-200 21 are downregulated and miRNA-21, 22 miRNA-199a, 23 and miRNA-145 24 are upregulated in lungs of IPF patients. Alterations in these miRNAs have also been demonstrated in lung fibroblasts or alveolar epithelial cells from IPF patients and pulmonary fibrosis animal models.…”