A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury
A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury
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DOI：
10.1096/fj.201600840r
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发表时间：
2017-02-01
期刊：
影响因子：
4.8
通讯作者：
Chen, Zheng
中科院分区：
文献类型：
--
作者：
Ren, Xiaomeng;Li, Xinzhi;Chen, Zheng
有效和选择性的化学探针是发现人类疾病新疗法的宝贵工具。nf - b诱导激酶（NIK）是肝损伤和纤维化发展的关键触发因素。化学探针抑制NIK活性是否能改善肝脏炎症和损伤在很大程度上是未知的。本研究发现，NIK的一种小分子抑制剂B022是肝脏炎症和损伤的一种有效的选择性化学探针。B022在体外和体内均抑制NIK信号通路，包括NIK诱导的p100- p52加工和炎症基因表达。此外，体内给药B022不仅可以预防NIK，还可以预防ccl4诱导的肝脏炎症和损伤。我们的数据表明，抑制NIK是一种治疗肝脏炎症、氧化应激和损伤的新策略。-任晓东，李晓东，贾磊，陈丹，侯慧，芮磊，赵艳，陈忠，一种nf - κ b诱导激酶（NIK）的小分子抑制剂保护肝脏免受毒素诱导的炎症、氧化应激和损伤。
Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF-B-inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown. In this study, a small-molecule inhibitor of NIK, B022, was found to be a potent and selective chemical probe for liver inflammation and injury. B022 inhibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing and inflammatory gene expression, both in vitro and in vivo. Furthermore, in vivo administration of B022 protected against not only NIK but also CCl4-induced liver inflammation and injury. Our data suggest that inhibition of NIK is a novel strategy for treatment of liver inflammation, oxidative stress, and injury.-Ren, X., Li, X., Jia, L., Chen, D., Hou, H., Rui, L., Zhao, Y., Chen, Z. A small-molecule inhibitor of NF-kappa B-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.