A small-molecule inhibitor of NF-kappa B-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury

doi:10.1096/fj.201600840R

	A small-molecule inhibitor of NF-kappa B-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury
	Ren, Xiaomeng 1; Li, Xinzhi 1; Jia, Linna 1; Chen, Deheng 2; Hou, Hai 3; Rui, Liangyou 4; Zhao, Yujun2 ; Chen, Zheng 1
刊名	FASEB JOURNAL
	2017-02
卷号	31 期号:2 页码:711-718
关键词	NIK liver injury inflammation CCl4
ISSN号	0892-6638
DOI	10.1096/fj.201600840R
文献子类	Article
英文摘要	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.
资助项目	Changbai Mountain Scholars Program of The People's Government of Jilin Province Grant[2013046] ; Jilin Science and Technology Development Program Grant[20160101204JC] ; Jilin Talent Development Foundation Grant[111860000] ; Fok Ying Tong Education Foundation Grant[151022] ; National Natural Science Foundation of China Grants[31500957] ; National Natural Science Foundation of China Grants[31671225] ; startup funds from Northeast Normal University[120401204] ; Shanghai Institute of Materia Medica startup grant[00000000] ; Young Overseas High-Level Talents Introduction Plan from the Chinese government[00000000]
WOS关键词	REGULATES GLUCOSE-METABOLISM ; CARBON-TETRACHLORIDE ; HEPATIC-FIBROSIS ; INSULIN-RESISTANCE ; SIGNALING PATHWAY ; IKK-ALPHA ; RAT-LIVER ; ACTIVATION ; MICE ; EXPRESSION
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
语种	英语
出版者	FEDERATION AMER SOC EXP BIOL
WOS记录号	WOS:000394235400023
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275641]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Zhao, Yujun; Chen, Zheng
作者单位	1.Northeast Normal Univ, Sch Life Sci, Key Lab Mol Epigenet, Minist Educ, Changchun, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Met Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Northwestern Polytech Univ, Sch Life Sci, Key Lab Space Bioscience & Biotechnol, Xian, Peoples R China; 4.Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
推荐引用方式 GB/T 7714	Ren, Xiaomeng,Li, Xinzhi,Jia, Linna,et al. A small-molecule inhibitor of NF-kappa B-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury[J]. FASEB JOURNAL,2017,31(2):711-718.
APA	Ren, Xiaomeng.,Li, Xinzhi.,Jia, Linna.,Chen, Deheng.,Hou, Hai.,...&Chen, Zheng.(2017).A small-molecule inhibitor of NF-kappa B-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.FASEB JOURNAL,31(2),711-718.
MLA	Ren, Xiaomeng,et al."A small-molecule inhibitor of NF-kappa B-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury".FASEB JOURNAL 31.2(2017):711-718.