HSP27 regulates TGF-β mediated lung fibroblast differentiation through the Smad3 and ERK pathways
HSP27 regulates TGF-β mediated lung fibroblast differentiation through the Smad3 and ERK pathways
复制标题
HSP27 通过 Smad3 和 ERK 途径调节 TGF-β 介导的肺成纤维细胞分化
DOI：
10.3892/ijmm.2016.2813
复制
发表时间：
2017-01-01
影响因子：
5.4
通讯作者：
Sun, Xia
中科院分区：
文献类型：
--
作者：
Wang, Gang;Jiao, Hao;Sun, Xia
特发性肺纤维化（IPF）是一种慢性致死性肺间质性疾病，病因不明。近年来研究表明，热休克蛋白27 （HSP27）通过调控上皮-间质转化（EMT）参与IPF的发病机制。然而，到目前为止，至少就我们所知，还没有研究成纤维细胞中HSP27在肺纤维化过程中的表达和作用。在这项研究中，我们检测了HSP27在博来霉素（BLM）攻击小鼠和转化生长因子- β (tgf - β)处理的人肺成纤维细胞的纤维化肺组织和成纤维细胞中的表达。结果显示，HSP27在blm攻击小鼠的纤维化肺组织和成纤维细胞中的表达显著升高。体外实验中，tgf - β刺激人肺成纤维细胞中HSP27的表达和分化。抑制Smad3或核因子κ B p65亚基的表达可减弱tgf - β诱导的HSP27表达的增加和人肺成纤维细胞的分化。此外，抑制HSP27表达可减弱tgf - β诱导的ERK和Smad3的活化，抑制人肺成纤维细胞的分化。总的来说，我们的研究结果表明，在肺纤维化过程中，HSP27在肺成纤维细胞中表达上调，随后HSP27通过Smad3和ERK途径调节肺成纤维细胞的分化。
Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease with unknown etiology. Recent studies have indicated that heat-shock protein 27 (HSP27) contributes to the pathogenesis of IPF through the regulation of epithelial-mesenchymal transition (EMT). However, the expression and role of HSP27 in fibroblasts during pulmonary fibrogenesis has not been investigated to date, at least to the best of our knowledge. In this study, we examined the expression of HSP27 in fibrotic lung tissue and fibroblasts from bleomycin (BLM)-challenged mice and human lung fibroblasts treated with transforming growth factor-beta (TGF-beta). The results revealed that the expression of HSP27 was significantly increased in fibrotic lung tissue and fibroblasts from BLM-challenged mice. In vitro, TGF-beta stimulated HSP27 expression in and the differentiation of human lung fibroblasts. The knockdown of Smad3 expression or nuclear factor-kappa B p65 subunit attenuated the TGF-beta-induced increase in HSP27 expression and the differentiation of human lung fibroblasts. In addition, the knockdown of HSP27 expression attenuated the TGF-beta-induced activation of ERK and Smad3, and inhibited the differentiation of human lung fibroblasts. On the whole, the findings of our study demonstrate that HSP27 expression is upregulated in lung fibroblasts during pulmonary fibrosis, and subsequently, HSP27 modulates lung fibroblast differentiation through the Smad3 and ERK pathways.