肺纤维化
博莱霉素
基因沉默
癌症研究
基因敲除
特发性肺纤维化
纤维化
上皮-间质转换
转化生长因子
成纤维细胞
肺
生物
化学
病理
细胞生物学
下调和上调
医学
内科学
细胞培养
基因
生物化学
遗传学
化疗
作者
Wenjing Deng,Yalong Zhang,Ping Fang,Hongyang Shi,Shuanying Yang
摘要
Abstract Idiopathic pulmonary fibrosis (IPF) is an interstitial pulmonary disease with slow onset and high mortality. Epithelial–mesenchymal transition (EMT) is a significant condition for tissue fibrosis, and lncRNA‐Snhg6 (small nucleolar RNA host gene 6) is related to EMT in some cancer cells, but its role in pulmonary fibrosis remains obscure. Here, we found that TGF‐β1 and Snhg6 were up‐regulated in lung tissues of BLM‐induced lung fibrosis mouse, and Snhg6 expression was significantly increased in primary lung fibroblasts after BLM treatment. Snhg6 knockdown notably alleviated the pulmonary dysfunction, and the increase of fibrosis area and collagen deposition induced by BLM. MiR‐26a‐5p was downregulated in BLM‐induced fibrotic lung tissues, and it was negatively regulated by Snhg6. Silencing Snhg6 markedly alleviated the TGF‐β1‐induced increase in fibrotic marker expression, cell proliferation, migration and differentiation, as well as the nuclear transport of p‐Smad2/3 by modulating miR‐26a‐5p expression in mouse lung fibroblasts. Moreover, overexpressing Snhg6‐induced collagen accumulation and fibroblast activation in fibroblasts, which was reversed by treatment with miR‐26a‐5p mimic or oxymatrine (an inhibitor of TGF‐β1‐Smads pathway). Interestingly, silencing Snhg6 in vivo mitigated BLM‐driven pulmonary fibrosis by regulating the miR‐26a‐5p/TGF‐β1‐Smads axis. Our data revealed that Snhg6 contributed to the process of BLM‐driven lung fibrosis in mouse by modulating the miR‐26a‐5p/TGF‐β1‐Smads axis, suggesting that Snhg6 might be a therapeutic target for lung fibrosis.
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