Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis.
Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis.
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DOI：
10.1038/cddis.2014.207
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发表时间：
2014-05-22
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
特发性肺纤维化（IPF）是一种慢性、进行性、高致死性纤维化肺病，治疗不良，病因不明。新出现的证据表明，上皮-间质转化（EMT）在肺纤维化期间上皮损伤后的修复和瘢痕形成中起重要作用。虽然一些mirna在IPF的病理生理过程中被证明是失调的，但关于EMT中mirna参与肺纤维化的研究有限。在我们的研究中，我们鉴定并构建了IPF mirna和EMT基因差异表达的调控网络。此外，我们发现miR-26a在实验性肺纤维化小鼠中下调。进一步研究表明，miR-26a调控HMGA2， HMGA2是EMT过程中的关键因子，也是调控网络中调控mirna数量最多的。更重要的是，在体外和体内，抑制miR-26a导致肺上皮细胞转化为肌成纤维细胞，而在A549细胞和小鼠中，强迫表达miR-26a分别减轻了TGF-β1-和blm诱导的EMT。综上所述，我们的研究揭示了miR-26a在肺纤维化EMT发病机制中的重要作用，并提示miR-26a可能是IPF的潜在治疗靶点。
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.
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影响因子：
4
作者：
Sonnylal, Sonali;Xu, Shiwen;de Crombrugghe, Benoit
通讯作者：
de Crombrugghe, Benoit
影响因子：
9
作者：
Chen, Y-L;Zhang, X.;Bai, J.;Gai, L.;Ye, X-L;Zhang, L.;Xu, Q.;Zhang, Y-X;Xu, L.;Li, H-P;Ding, X.
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影响因子：
20.1
作者：
Icli B;Wara AK;Moslehi J;Sun X;Plovie E;Cahill M;Marchini JF;Schissler A;Padera RF;Shi J;Cheng HW;Raghuram S;Arany Z;Liao R;Croce K;MacRae C;Feinberg MW
通讯作者：
Feinberg MW
DOI：
10.1152/ajplung.00149.2013
发表时间：
2014-03-01
影响因子：
4.9
作者：
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通讯作者：
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影响因子：
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作者：
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