Journal
FASEB JOURNAL
Volume 31, Issue 2, Pages 711-718Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201600840R
Keywords
NIK; liver injury; inflammation; CCl4
Categories
Funding
- 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, 31671225]
- startup funds from Northeast Normal University [120401204]
- Shanghai Institute of Materia Medica startup grant
- Young Overseas High-Level Talents Introduction Plan from the Chinese government
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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.
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