中国药理学通报2017，Vol.33Issue(5)：630-636,7.DOI:10.3969/j.issn.1001-1978.2017.05.009
雷公藤内酯醇减少放射性肺纤维化中肌成纤维细胞活化与抑制TGF-β1/ERK/Smad3通路相关
TPL's suppression on activation of myofibroblasts in radiation induced lung fibrosis related to its inhibition on TGF-β1/ERK/Smad3 pathway
摘要
Abstract
Aim To observe the correlation between the TPL's suppression on myofibrolbasts(MFBs)activation and TGF-β1/ERK/Smad3 pathway by performing in vivo and in vitro experiments.Methods In vitro model of MFBs activation was set up by stimulating fibroblasts with TGF-β1,and in vivo model of MFBs activation in radiated lung tissue was built by thoracic radiation on C57BL/6 mice.MFBs activation was analyzed by detecting the expression of α-SMA(using RT-PCR and Western blot)and Col Ⅰ(using RT-PCR and ELISA methods).The levels of p-ERK,p-Smad3(Ser208)and p-Smad3(Ser423)were measured by Western blot.ERK siRNA and Smad3 siRNA were used to observe the status of ERK and Smad3 in MFBs activation.Results TGF-β1 activated p-ERK/p-Smad3(Ser208)and p-Smad3(Ser423),increased the expression of α-SMA and synthesis of Col Ⅰ,which indicated MFBs activation.siRNA knockdown assay showed that both ERK and Smad3 were involved in regulating the levels of α-SMA and Col Ⅰ,and ERK influenced MFBs transformation possibly through its phosphorylation of Smad3(Ser208).TPL treatment inhibited the phosphorylation activation of ERK,Smad3(Ser208),Smad3(Ser423)in vitro and in vivo,therefore significantly reduced the level of α-SMA and Col Ⅰ,and the number of activated MFBs was decreased.Conclusion TPL mitigates radiation-induced pulmonary fibrosis by inhibiting the activation of MFBs,which is partly through suppressing TGF-β1/ERK/Smad3 pathway.关键词
雷公藤内酯醇/放射性肺纤维化/肌成纤维细胞/α-平滑肌肌动蛋白/Ⅰ型胶原蛋白/转化生长因子β1/ERK/Smad3Key words
triptolide/radiation induced pulmonary fibrosis/myofibroblast/α-smooth muscle actin/type Ⅰ collagen/transforming growth factor β1(TGF-β1)/ERK/Smad3分类
医药卫生引用本文复制引用
张彦伟,张志强,吴丽贤,张鲁榕,陈纯..雷公藤内酯醇减少放射性肺纤维化中肌成纤维细胞活化与抑制TGF-β1/ERK/Smad3通路相关[J].中国药理学通报,2017,33(5):630-636,7.基金项目
国家自然科学基金资助项目(No81473264) （No81473264）
福建省卫生厅中医药科研项目(Nowzze201308) （Nowzze201308）
福建省自然科学基金面上项目(No2014J01336) （No2014J01336）
