ERp57通过影响成纤维细胞活化参与特发性肺纤维化疾病发生发展

ERp57 regulates development of idiopathic pulmonary fibrosis by suppressing fibroblast activation

目的探究ERp57对成纤维细胞活化的影响及揭示其在肺纤维化发生发展中的作用及机制。方法实验性研究。采用免疫组织化学染色及蛋白质印迹检测特发性肺纤维化患者和博来霉素诱导的小鼠肺纤维化肺组织中ERp57的表达情况。体外培养肺原代成纤维细胞,将ERp57-siRNA脂质体转染成纤维细胞,蛋白质印迹检测siRNA干扰ERp57表达对成纤维细胞活化的影响。结果在特发性肺纤维化患者和博来霉素诱导的小鼠肺纤维化肺组织中,ERp57表达水平显著上调,且主要表达于成纤维细胞中;体外实验发现人原代成纤维细胞经转化生长因子β1刺激后,ERp57表达水平呈时间依赖性升高。同时,干扰ERp57的表达可明显抑制成纤维细胞活化。结论ERp57与肺纤维化的发生发展密切相关,抑制ERp57的表达可显著抑制成纤维细胞的活化。

Objective To explore the effects of ERp57 on fibroblast activation and its function and mechanism in the pathogenesis of pulmonary fibrosis.Methods Immunohistochemical staining and Western blot were used to detect the expression level of ERp57 in lung tissues of idiopathic pulmonary fibrosis patients and bleomycin-induced pulmonary fibrosis in mice.In vitro,primary lung fibroblasts were cultured and ERp57-siRNA liposomes were transfected into fibroblasts.Western blot was used to detect the effect of siRNA interference with ERp57 expression on the activation of fibroblasts.Results In the lung tissues of idiopathic pulmonary fibrosis patients and bleomycin-induced pulmonary fibrosis mice,the expression level of ERp57 was significantly up-regulated,and it was mainly expressed in fibroblasts.In vitro,experiments revealed that the expression level of ERp57 increased in a time-dependent manner in human primary fibroblasts after transforming growth factor-β1 stimulation.In line with those results,knockdown of ERp57 expression can significantly inhibit fibroblast activation.Conclusions ERp57 is closely related to the pathogenesis of pulmonary fibrosis and suppression of ERp57 expression can significantly inhibit the activation of fibroblasts.