Triptolide alleviates radiation-induced pulmonary fibrosis via inhibiting IKKβ stimulated LOX production
Triptolide alleviates radiation-induced pulmonary fibrosis via inhibiting IKKβ stimulated LOX production
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DOI：
10.1016/j.bbrc.2020.04.023
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
陈纯
中科院分区：
文献类型：
--
作者：
郭凯宁;陈金燃;陈张杰;罗格莲;杨善民;张美;洪金省;张鲁榕;陈纯
Lysyl oxidase (LOX) is involved in fibrosis by catalyzing collagen cross-linking. Previous work observed that Triptolide (TPL) alleviated radiation-induced pulmonary fibrosis (RIPF), but it is unknown whether the anti-RIPF effect of TPL is related to LOX. In a mouse model of RIPF, we found that LOX persistently increased in RIPF which was significantly lowered by TPL. Excessive LOX aggravated fibrotic lesions in RIPF, while LOX inhibition mitigated RIPF. Irradiation enhanced the transcription and synthesis of LOX by lung fibroblasts through IKKβ/NFκB activation, and siRNA knockdown IKKβ largely abolished LOX production. By interfering radiation induced IKKβ activation, TPL prevented NFκB nuclear translocation and DNA binding, and potently decreased LOX synthesis. Our results demonstrate that the anti-RIPF effect of TPL is associated with reduction of LOX production which mediated by inhibition of IKKβ/NFκB pathway.
