TPL's suppression on activation of myofibroblasts in radiation induced lung fibrosis related to its inhibition on TGF-β1/ERK/Smad3 pathway
10.3969/j.issn.1001-1978.2017.05.009
- VernacularTitle: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
- Author:
Yanwei ZHANG
;
Zhiqiang ZHANG
;
Lixian WU
;
Lurong ZHANG
;
Chun CHEN
- Keywords:
triptolide;
radiation induced pulmonary fibrosis;
myofibroblast;
α-smooth muscle actin;
type Ⅰ collagen;
transforming growth factor β1(TGF-β1);
ERK;
Smad3
- From:
Chinese Pharmacological Bulletin
2017;33(5):630-636
- CountryChina
- Language:Chinese
-
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.
