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

dc.contributor.authorRen, Xiaomeng
dc.contributor.authorLi, Xinzhi
dc.contributor.authorJia, Linna
dc.contributor.authorChen, Deheng
dc.contributor.authorHou, Hai
dc.contributor.authorRui, Liangyou
dc.contributor.authorZhao, Yujun
dc.contributor.authorChen, Zheng
dc.date.accessioned2020-03-17T18:32:00Z
dc.date.available2020-03-17T18:32:00Z
dc.date.issued2017-02
dc.identifier.citationRen, Xiaomeng; Li, Xinzhi; Jia, Linna; Chen, Deheng; Hou, Hai; Rui, Liangyou; Zhao, Yujun; Chen, Zheng (2017). "A small‐molecule inhibitor of NF‐κB‐inducing kinase (NIK) protects liver from toxin‐induced inflammation, oxidative stress, and injury." The FASEB Journal 31(2): 711-718.
dc.identifier.issn0892-6638
dc.identifier.issn1530-6860
dc.identifier.urihttps://hdl.handle.net/2027.42/154426
dc.description.abstractPotent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF‐κβ‐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‐κβ‐inducing kinase (NIK) protects liver from toxin‐induced inflammation, oxidative stress, and injury. FASEB J. 31, 711–718 (2017). http://www.fasebj.org
dc.publisherFederation of American Societies for Experimental Biology
dc.publisherWiley Periodicals, Inc.
dc.subject.otherinflammation
dc.subject.otherCCl4
dc.subject.otherNIK
dc.subject.otherliver injury
dc.titleA small‐molecule inhibitor of NF‐κB‐inducing kinase (NIK) protects liver from toxin‐induced inflammation, oxidative stress, and injury
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelBiology
dc.subject.hlbtoplevelScience
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/154426/1/fsb2fasebj3120840r.pdf
dc.identifier.doi10.1096/fj.201600840R
dc.identifier.sourceThe FASEB Journal
dc.identifier.citedreferenceChen, Z., Morris, D. L., Jiang, L., Liu, Y., and Rui, L. ( 2014 ) SH2B1 in β‐cells promotes insulin expression and glucose metabolism in mice. Mol. Endocrinol. 28, 696 – 705
dc.identifier.citedreferenceBerger, M. L., Bhatt, H., Combes, B., and Estabrook, R. W. ( 1986 ) CCl4‐induced toxicity in isolated hepatocytes: the importance of direct solvent injury. Hepatology 6, 36 – 45
dc.identifier.citedreferenceLee, I.‐C., Kim, S.‐H., Baek, H.‐S., Moon, C., Kang, S.‐S., Kim, S.‐H., Kim, Y.‐B., Shin, I.‐S., and Kim, J.‐C. ( 2014 ) The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride‐induced hepatic oxidative damage and inflammatory response in rats. Food Chem. Toxicol. 63, 174 – 185
dc.identifier.citedreferenceKovalovich, K., DeAngelis, R. A., Li, W., Furth, E. E., Ciliberto, G., and Taub, R. ( 2000 ) Increased toxin‐induced liver injury and fibrosis in interleukin‐6‐deficient mice. Hepatology 31, 149 – 159
dc.identifier.citedreferenceCzaja, M. J., Xu, J., and Alt, E. ( 1995 ) Prevention of carbon tetrachloride‐induced rat liver injury by soluble tumor necrosis factor receptor. Gastroenterology 108, 1849 – 1854
dc.identifier.citedreferenceSlater, T. F. ( 1966 ) Necrogenic action of carbon tetrachloride in the rat: a speculative mechanism based on activation. Nature 209, 36 – 40
dc.identifier.citedreferenceShi, J., Aisaki, K., Ikawa, Y., and Wake, K. ( 1998 ) Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am. J. Pathol. 153, 515 – 525
dc.identifier.citedreferenceShen, H., Sheng, L., Chen, Z., Jiang, L., Su, H., Yin, L., Omary, M. B., and Rui, L. ( 2014 ) Mouse hepatocyte overexpression of NF‐κB inducing kinase (NIK) triggers fatal macrophage‐dependent liver injury and fibrosis. Hepatology 60, 2065 – 2076
dc.identifier.citedreferenceJiang, B., Shen, H., Chen, Z., Yin, L., Zan, L., and Rui, L. ( 2015 ) Carboxyl terminus of HSC70‐interacting protein (CHIP) down‐regulates NF‐κβ‐inducing kinase (NIK) and suppresses NIK‐induced liver injury. J. Biol. Chem. 290, 11704–11714
dc.identifier.citedreferenceXiao, G., Fong, A., and Sun, S.‐C. ( 2004 ) Induction of p100 processing by NF‐kappaβ‐inducing kinase involves docking IkappaB kinase a (IKKalpha) to p100 and IKKalpha‐mediated phosphorylation. J. Biol. Chem. 279, 30099–30105
dc.identifier.citedreferenceXiao, G., Harhaj, E. W., and Sun, S. C. ( 2001 ) NF‐kappa β‐inducing kinase regulates the processing of NF‐kappaB2 p100. Mol. Cell 7, 401 – 409
dc.identifier.citedreferenceSenftleben, U., Cao, Y., Xiao, G., Greten, F. R., Krähn, G., Bonizzi, G., Chen, Y., Hu, Y., Fong, A., Sun, S. C., and Karin, M. ( 2001 ) Activation by IKKalpha of a second, evolutionary conserved, NF‐kappa B signaling pathway. Science 293, 1495 – 1499
dc.identifier.citedreferenceSun, S. C. ( 2011 ) Non‐canonical NF‐κB signaling pathway. Cell Res. 21, 71 – 85
dc.identifier.citedreferenceDe Leon‐Boenig, G., Bowman, K. K., Feng, J. A., Crawford, T., Everett, C., Franke, Y., Oh, A., Stanley, M., Staben, S. T., Starovasnik, M. A., Wallweber, H. J., Wu, J., Wu, L. C., Johnson, A. R., and Hymowitz, S. G. ( 2012 ) The crystal structure of the catalytic domain of the NF‐κB inducing kinase reveals a narrow but ~exible active site. Structure 20, 1704 – 1714
dc.identifier.citedreferenceDemchenko, Y. N., Brents, L. A., Li, Z., Bergsagel, L. P., McGee, L. R., and Kuehl, M. W. ( 2014 ) Novel inhibitors are cytotoxic for myeloma cells with NFkB inducing kinase‐dependent activation of NFkB. Oncotarget 5, 4554 – 4566
dc.identifier.citedreferenceChen, G., Cushing, T. D., Fisher, B., He, X., Li, K., Li, Z., McGee, L. R., Pattaropong, V., Faulder, P., Seganish, J. L., Shin, Y. Alkylnyl alcohols as kinase inhibitors. PCT Patent Publication WO 2009159011, December 30, 2009
dc.identifier.citedreferenceQin, W., Li, X., Xie, L., Li, S., Liu, J., Jia, L., Dong, X., Ren, X., Xiao, J., Yang, C., Zhou, Y., and Chen, Z. ( 2016 ) A long non‐coding RNA, APOA4‐AS, regulates APOA4 expression depending on HuR in mice. Nucleic Acids Res. 44, 6423 – 6433
dc.identifier.citedreferenceChen, Z., Canet, M. J., Sheng, L., Jiang, L., Xiong, Y., Yin, L., and Rui, L. ( 2015 ) Hepatocyte TRAF3 promotes insulin resistance and type 2 diabetes in mice with obesity. Mol. Metab. 4, 951 – 960
dc.identifier.citedreferenceChen, Z., Sheng, L., Shen, H., Zhao, Y., Wang, S., Brink, R., and Rui, L. ( 2012 ) Hepatic TRAF2 regulates glucose metabolism through enhancing glucagon responses. Diabetes 61, 566 – 573
dc.identifier.citedreferenceChen, Z., Shen, H., Sun, C., Yin, L., Tang, F., Zheng, P., Liu, Y., Brink, R., and Rui, L. ( 2015 ) Myeloid cell TRAF3 promotes metabolic inflammation, insulin resistance, and hepatic steatosis in obesity. Am. J. Physiol. Endocrinol. Metab. 308, E460 – E469
dc.identifier.citedreferenceChen, Z., Morris, D. L., Jiang, L., Liu, Y., and Rui, L. ( 2014 ) SH2B1 in β‐cells regulates glucose metabolism by promoting β‐cellsurvivaland islet expansion. Diabetes 63, 585 – 595
dc.identifier.citedreferenceCubero, F. J., Zhao, G., Nevzorova, Y. A., Hatting, M., Al Masaoudi, M., Verdier, J., Peng, J., Schaefer, F. M., Hermanns, N., Boekschoten, M. V., Grouls, C., Gassler, N., Kiessling, F., Muller, M., Davis, R. J., Liedtke, C., and Trautwein, C. ( 2015 ) Haematopoietic cell‐derived Jnk1 is crucial for chronic inflammation and carcinogenesis in an experimental model of liver injury. J. Hepatol. 62, 140 – 149
dc.identifier.citedreferenceKluwe, J., Pradere, J.‐P., Gwak, G.‐Y., Mencin, A., De Minicis, S., Osterreicher, C. H., Colmenero, J., Bataller, R., and Schwabe, R. F. ( 2010 ) Modulation of hepatic fibrosis by c‐Jun‐N‐terminal kinase inhibition. Gastroenterology 138, 347 – 359
dc.identifier.citedreferenceArmendáriz‐Borunda, J., Islas‐Carbajal, M. C., Meza‐García, E., Rincón, A. R., Lucano, S., Sandoval, A. S., Salazar, A., Berumen, J., Alvarez, A., Covarrubias, A., Aréchiga, G., and García, L. ( 2006 ) A pilot study in patients with established advanced liver fibrosis using pirfenidone. Gut 55, 1663 – 1665
dc.identifier.citedreferenceFagone, P., Mangano, K., Pesce, A., Portale, T. R., Puleo, S., and Nicoletti, F. ( 2016 ) Emerging therapeutic targets for the treatment of hepatic fibrosis. Drug Discov. Today 21, 369 – 375
dc.identifier.citedreferenceRockey, D. C., and Chung, J. J. ( 1994 ) Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis. J. Investig. Med. 42, 660 – 670
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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