FOXO4 D-Retro-Inverso影响细胞外基质的产生并缓解肺纤维化
FOXO4-D-Retro-Inverso targets extracellular matrix production and ameliorates pulmonary fibrosis
刘颖 1后钦珲 1王睿 1刘媛 1吴开松 1杨亦斌 1程真顺1
作者信息
- 1. 武汉大学中南医院呼吸与危重症医学科 湖北 武汉 430071
- 折叠
摘要
目的:观察FOXO4 D-Retro-Inverso(FOXO4-DRI)对肺纤维化小鼠模型及肺成纤维细胞活化和细胞外基质(ECM)生成的影响.方法:C57BL/6J雄鼠气管内滴注博来霉素构建肺纤维化模型,予以FOXO4-DRI治疗,第 21 天观察肺结构改变及纤维化标志物的表达水平.人肺成纤维细胞 MRC5 予以 TGF-β1 刺激后给予FOXO4-DRI干预,检测成纤维细胞活化标志物及ECM表达水平.结果:气管内滴注博来霉素后成功诱导小鼠肺部结构破坏,纤维化评分升高(P<0.01),肺纤维化标志物表达量升高(P<0.01).FOXO4-DRI治疗后小鼠肺部结构损坏减轻,纤维化评分降低(P<0.01),肺纤维化标志物表达降低(P<0.01).TGF-β1诱导成纤维细胞活化标志物及ECM表达升高(P<0.01),给予FOXO4-DRI干预后上述分子表达下降(P<0.01).结论:FOXO4-DRI抑制肺成纤维细胞活化及ECM产生而改善小鼠肺纤维化.
Abstract
Objective:To investigate the effect of FOXO4 D-Retro-Inverso(FOXO4-DRI)on pulmonary fi-brosis of mice,fibroblast activation,and extracellular matrix(ECM)production.Methods:C57BL/6J male mice received intratracheal injection with bleomycin to induce pulmonary fibrosis,then treated with FOXO4-DRI,and lung tissues were obtained after 21 days.Lung structural changes and the expression of pulmonary fibrosis markers were observed.MRC5 was stimulated with TGF-β1 followed by FOXO4-DRI intervention,and then fibroblast activation markers and ECM proteins were detected.Results:Bleomycin-induced mice showed obvious structural changes,higher fibrosis scores(P<0.01),and elevated expression of pulmonary fibrosis markers(P<0.01).While FOXO4-DRI-treated mice showed alleviative structural changes and lower fibrosis scores(P<0.01),and lower expression of pulmonary fibrosis markers(P<0.01).TGF-β1 induced fibroblast activation and increased the level of ECM proteins(P<0.01),which was alleviated by FOXO4-DRI interven-tion(P<0.01).Conclusion:FOXO4-DRI inhibits the activation of lung fibroblasts and production of ECM proteins,thereby ameliorates lung fibrosis in mice.
关键词
肺纤维化/细胞外基质/FOXO4/D-Retro-Inverso/成纤维细胞/博莱霉素Key words
Pulmonary Fibrosis/Extracellular Matrix/FOXO4 D-Retro-Inverso/Fibroblast/Bleomycin引用本文复制引用
基金项目
国家自然科学基金资助项目(82070062)
出版年
2024
NETL
NSTL
万方数据