炎症
上睑下垂
细胞生物学
化学
癌症研究
生物
药理学
炎症体
免疫学
作者
Fenghao Geng,Zhong Li,Ting Yang,Jianhui Chen,Ping Yang,Fengdi Jiang,Tao Yan,Bin Song,Zuxiang Yü,Daojiang Yu,Jie Zhang,Jianping Cao,Shuyu Zhang
标识
DOI:10.1002/advs.202306253
摘要
Abstract The extensive application of nuclear technology has increased the potential of uncontrolled radiation exposure to the public. Since skin is the largest organ, radiation‐induced skin injury remains a serious medical concern. Organisms evolutionally develop distinct strategies to protect against environment insults and the related research may bring novel insights into therapeutics development. Here, 26 increased peptides are identified in skin tissues of frogs ( Pelophylax nigromaculatus ) exposed to electron beams, among which four promoted the wound healing of irradiated skin in rats. Specifically, radiation‐induced frog skin peptide‐2 (RIFSP‐2), from histone proteolysis exerted membrane permeability property, maintained cellular homeostasis, and reduced pyroptosis of irradiated cells with decreased TBK1 phosphorylation. Subsequently, stearyl‐CoA desaturase 1 (SCD1) is identified, a critical enzyme in biogenesis of monounsaturated fatty acids (MUFAs) as a direct target of RIFSP‐2 based on streptavidin‐biotin system. The lipidomic analysis further assured the restrain of MUFAs biogenesis by RIFSP‐2 following radiation. Moreover, the decreased MUFA limited radiation‐induced and STING‐mediated inflammation response. In addition, genetic depletion or pharmacological inhibition of STING counteracted the decreased pyroptosis by RIFSP‐2 and retarded tissue repair process. Altogether, RIFSP‐2 restrains radiation‐induced activation of SCD1‐MUFA‐STING axis. Thus, the stress‐induced amphibian peptides can be a bountiful source of novel radiation mitigators.
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