{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:29:59Z","timestamp":1793042999890,"version":"4.5.0"},"reference-count":97,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T00:00:00Z","timestamp":1656720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China Grant","doi-asserted-by":"publisher","award":["92057110"],"award-info":[{"award-number":["92057110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China Grant","doi-asserted-by":"publisher","award":["31971083"],"award-info":[{"award-number":["31971083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China Grant","doi-asserted-by":"publisher","award":["LQ2020022"],"award-info":[{"award-number":["LQ2020022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China Grant","doi-asserted-by":"publisher","award":["17YQ01"],"award-info":[{"award-number":["17YQ01"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Scientists Nurturing Program from the Department of Education of Liaoning Province","award":["92057110"],"award-info":[{"award-number":["92057110"]}]},{"name":"Young Scientists Nurturing Program from the Department of Education of Liaoning Province","award":["31971083"],"award-info":[{"award-number":["31971083"]}]},{"name":"Young Scientists Nurturing Program from the Department of Education of Liaoning Province","award":["LQ2020022"],"award-info":[{"award-number":["LQ2020022"]}]},{"name":"Young Scientists Nurturing Program from the Department of Education of Liaoning Province","award":["17YQ01"],"award-info":[{"award-number":["17YQ01"]}]},{"name":"305 Hospital of People\u2019s Liberation Army Research Grant","award":["92057110"],"award-info":[{"award-number":["92057110"]}]},{"name":"305 Hospital of People\u2019s Liberation Army Research Grant","award":["31971083"],"award-info":[{"award-number":["31971083"]}]},{"name":"305 Hospital of People\u2019s Liberation Army Research Grant","award":["LQ2020022"],"award-info":[{"award-number":["LQ2020022"]}]},{"name":"305 Hospital of People\u2019s Liberation Army Research Grant","award":["17YQ01"],"award-info":[{"award-number":["17YQ01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Non-canonical nuclear factor kappa B (NF-\u03baB) signaling pathway regulates many physiological and pathological processes, including liver homeostasis and diseases. Recent studies demonstrate that non-canonical NF-\u03baB signaling pathway plays an essential role in hyperglycemia, non-alcoholic fatty liver disease, alcoholic liver disease, liver regeneration, liver injury, autoimmune liver disease, viral hepatitis, and hepatocellular carcinoma. Small-molecule inhibitors targeting to non-canonical NF-\u03baB signaling pathway have been developed and shown promising results in the treatment of liver injuries. Here, the recent advances and future prospects in understanding the roles of the non-canonical NF-\u03baB signaling pathways in the regulation of liver diseases are discussed.<\/jats:p>","DOI":"10.3390\/molecules27134275","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T20:59:18Z","timestamp":1656968358000},"page":"4275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Progress and Prospects of Non-Canonical NF-\u03baB Signaling Pathway in the Regulation of Liver Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"Li","family":"Tao","sequence":"first","affiliation":[{"name":"Emergency Department, 305 Hospital of People\u2019s Liberation Army, Beijing 100017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical and Biology Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Zhai","sequence":"additional","affiliation":[{"name":"Emergency Department, 305 Hospital of People\u2019s Liberation Army, Beijing 100017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7129-6644","authenticated-orcid":false,"given":"Zheng","family":"Chen","sequence":"additional","affiliation":[{"name":"HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.2337\/db11-0474","article-title":"Hepatic TRAF2 regulates glucose metabolism through enhancing glucagon responses","volume":"61","author":"Chen","year":"2012","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.molmet.2015.09.013","article-title":"Hepatocyte TRAF3 promotes insulin resistance and type 2 diabetes in mice with obesity","volume":"4","author":"Chen","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10592","DOI":"10.1038\/ncomms10592","article-title":"Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling","volume":"7","author":"Wang","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s12272-009-1714-z","article-title":"Suppression of hepatitis B virus-derived human hepatocellular carcinoma by NF-kappaB-inducing kinase-specific siRNA using liver-targeting liposomes","volume":"32","author":"Cho","year":"2009","journal-title":"Arch. Pharmacal. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1002\/hep.27348","article-title":"Mouse hepatocyte overexpression of NF-\u03baB-inducing kinase (NIK) triggers fatal macrophage-dependent liver injury and fibrosis","volume":"60","author":"Shen","year":"2014","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1096\/fj.201600840R","article-title":"A small-molecule inhibitor of NF-\u03baB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury","volume":"31","author":"Ren","year":"2017","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1021\/acs.jmedchem.0c00396","article-title":"Discovery of a Potent and Selective NF-\u03baB-Inducing Kinase (NIK) Inhibitor That Has Anti-inflammatory Effects In Vitro and In Vivo","volume":"63","author":"Li","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared principles in NF-kappaB signaling","volume":"132","author":"Hayden","year":"2008","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nri.2017.52","article-title":"The non-canonical NF-\u03baB pathway in immunity and inflammation","volume":"17","author":"Sun","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/ni.2065","article-title":"Crosstalk in NF-\u03baB signaling pathways","volume":"12","author":"Oeckinghaus","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/cr.2010.177","article-title":"Non-canonical NF-kappaB signaling pathway","volume":"21","author":"Sun","year":"2011","journal-title":"Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30099","DOI":"10.1074\/jbc.M401428200","article-title":"Induction of p100 Processing by NF-\u03baB-inducing Kinase Involves Docking I\u03baB Kinase \u03b1 (IKK\u03b1) to p100 and IKK\u03b1-mediated Phosphorylation","volume":"279","author":"Xiao","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S1097-2765(01)00187-3","article-title":"NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100","volume":"7","author":"Xiao","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1126\/science.1062677","article-title":"Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway","volume":"293","author":"Senftleben","year":"2001","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3164\/jcbn.12-115","article-title":"B cell activating factor in obesity is regulated by oxidative stress in adipocytes","volume":"52","author":"Tada","year":"2013","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/s41598-018-37403-y","article-title":"Depletion of B cell-activating factor attenuates hepatic fat accumulation in a murine model of nonalcoholic fatty liver disease","volume":"9","author":"Nakamura","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/labinvest.2012.176","article-title":"Blockade of B-cell-activating factor signaling enhances hepatic steatosis induced by a high-fat diet and improves insulin sensitivity","volume":"93","author":"Kawasaki","year":"2013","journal-title":"Lab Invest."},{"key":"ref_18","first-page":"319","article-title":"Elevation in Circulating Soluble CD40 Ligand Concentrations in Type 2 Diabetic Retinopathy and Association with its Severity","volume":"128","author":"Lamine","year":"2020","journal-title":"Exp. Clin. Endocrinol. Diabetes Off. J. Ger. Soc. Endocrinol. Ger. Diabetes Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E460","DOI":"10.1152\/ajpendo.00470.2014","article-title":"Myeloid cell TRAF3 promotes metabolic inflammation, insulin resistance, and hepatic steatosis in obesity","volume":"308","author":"Chen","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/nm.2756","article-title":"NF-\u03baB-inducing kinase (NIK) promotes hyperglycemia and glucose intolerance in obesity by augmenting glucagon action","volume":"18","author":"Sheng","year":"2012","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1210\/en.2016-1582","article-title":"Liver NF-\u03baB-Inducing Kinase Promotes Liver Steatosis and Glucose Counterregulation in Male Mice With Obesity","volume":"158","author":"Liu","year":"2017","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1161\/ATVBAHA.111.231357","article-title":"CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice","volume":"31","author":"Poggi","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E951","DOI":"10.1152\/ajpendo.00514.2012","article-title":"CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance","volume":"304","author":"Guo","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3579","DOI":"10.7150\/thno.40149","article-title":"NIK links inflammation to hepatic steatosis by suppressing PPAR\u03b1 in alcoholic liver disease","volume":"10","author":"Li","year":"2020","journal-title":"Theranostics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/hep.22597","article-title":"Lymphotoxin-beta receptor signaling regulates hepatic stellate cell function and wound healing in a murine model of chronic liver injury","volume":"49","author":"Ruddell","year":"2009","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1002\/hep4.1757","article-title":"Hepatic NF-\u03baB-Inducing Kinase and Inhibitor of NF-\u03baB Kinase Subunit \u03b1 Promote Liver Oxidative Stress, Ferroptosis, and Liver Injury","volume":"5","author":"Zhong","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.4049\/jimmunol.175.2.1295","article-title":"Contribution of the lymphotoxin beta receptor to liver regeneration","volume":"175","author":"Anders","year":"2005","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/hep.20520","article-title":"Differential lymphotoxin-beta and interferon gamma signaling during mouse liver regeneration induced by chronic and acute injury","volume":"41","author":"Akhurst","year":"2005","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/hep.23663","article-title":"Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells","volume":"52","author":"Viebahn","year":"2010","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Karaca, G., Swiderska-Syn, M., Xie, G., Syn, W.K., Kr\u00fcger, L., Machado, M.V., Garman, K., Choi, S.S., Michelotti, G.A., and Burkly, L.C. (2014). TWEAK\/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0083987"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e34152","DOI":"10.7554\/eLife.34152","article-title":"Hepatic NF-kB-inducing kinase (NIK) suppresses mouse liver regeneration in acute and chronic liver diseases","volume":"7","author":"Xiong","year":"2018","journal-title":"eLife"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4986","DOI":"10.3748\/wjg.v12.i31.4986","article-title":"Gene expression analysis of primary normal human hepatocytes infected with human hepatitis B virus","volume":"12","author":"Ryu","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ccr.2009.08.021","article-title":"A lymphotoxin-driven pathway to hepatocellular carcinoma","volume":"16","author":"Haybaeck","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1136\/gut.52.9.1327","article-title":"Upregulation of lymphotoxin beta expression in liver progenitor (oval) cells in chronic hepatitis C","volume":"52","author":"Lowes","year":"2003","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1126\/science.1243462","article-title":"Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA","volume":"343","author":"Lucifora","year":"2014","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1089\/jir.2014.0032","article-title":"Serum levels of B-cell activating factor in chronic hepatitis B virus infection: Association with clinical diseases","volume":"34","author":"Yang","year":"2014","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/hep.25966","article-title":"CD40 inhibits replication of hepatitis C virus in primary human hepatocytes by c-Jun N terminal kinase activation independent from the interferon pathway","volume":"57","author":"Rau","year":"2013","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1159\/000431150","article-title":"CD4+CD25+ Regulatory T Cells Inhibit Natural Killer Cell Hepatocytotoxicity of Hepatitis B Virus Transgenic Mice via Membrane-Bound TGF-\u03b2 and OX40","volume":"8","author":"Chen","year":"2016","journal-title":"J. Innate Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"eaah5766","DOI":"10.1126\/scitranslmed.aah5766","article-title":"An OX40\/OX40L interaction directs successful immunity to hepatitis B virus","volume":"10","author":"Publicover","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5797","DOI":"10.1073\/pnas.1502390112","article-title":"Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus","volume":"112","author":"Ebert","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.1073\/pnas.1502400112","article-title":"Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis","volume":"112","author":"Ebert","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","first-page":"e01617","article-title":"Hepatitis C Virus Infection Induces Hepatic Expression of NF-\u03baB-Inducing Kinase and Lipogenesis by Downregulating miR-122","volume":"10","author":"Lowey","year":"2019","journal-title":"mBio"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.canlet.2014.09.026","article-title":"Regulatory B cells accelerate hepatocellular carcinoma progression via CD40\/CD154 signaling pathway","volume":"355","author":"Shao","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_44","first-page":"136","article-title":"Plasma B-cell activating factor levels and polymorphisms in hepatitis B-related hepatocellular carcinoma: Clinical correlation and prognosis","volume":"39","author":"Khlaiphuengsin","year":"2021","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1245\/s10434-006-9277-4","article-title":"Receptor activator of nuclear factor-kappaB ligand (RANKL) expression in hepatocellular carcinoma with bone metastasis","volume":"14","author":"Sasaki","year":"2007","journal-title":"Ann. Surg. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e1404214","DOI":"10.1080\/2162402X.2017.1404214","article-title":"OX40 expression in hepatocellular carcinoma is associated with a distinct immune microenvironment, specific mutation signature, and poor prognosis","volume":"7","author":"Xie","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1038\/onc.2011.523","article-title":"MicroRNA-520e suppresses growth of hepatoma cells by targeting the NF-\u03baB-inducing kinase (NIK)","volume":"31","author":"Zhang","year":"2012","journal-title":"Oncogene"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/hep.21017","article-title":"CD4+ T cells contribute to postischemic liver injury in mice by interacting with sinusoidal endothelium and platelets","volume":"43","author":"Khandoga","year":"2006","journal-title":"Hepatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1002\/hep.23153","article-title":"CD4 T cells promote tissue inflammation via CD40 signaling without de novo activation in a murine model of liver ischemia\/reperfusion injury","volume":"50","author":"Shen","year":"2009","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bhogal, R.H., Weston, C.J., Curbishley, S.M., Adams, D.H., and Afford, S.C. (2012). Activation of CD40 with platelet derived CD154 promotes reactive oxygen species dependent death of human hepatocytes during hypoxia and reoxygenation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030867"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1097\/01.TP.0000161248.43481.A2","article-title":"The CD154-CD40 T-cell co-stimulation pathway in liver ischemia and reperfusion inflammatory responses","volume":"79","author":"Ke","year":"2005","journal-title":"Transplantation"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/00007890-200208150-00005","article-title":"CD154-CD40 T-cell costimulation pathway is required in the mechanism of hepatic ischemia\/reperfusion injury, and its blockade facilitates and depends on heme oxygenase-1 mediated cytoprotection","volume":"74","author":"Shen","year":"2002","journal-title":"Transplantation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.bbalip.2016.06.002","article-title":"Resolvin D1 protects the liver from ischemia\/reperfusion injury by enhancing M2 macrophage polarization and efferocytosis","volume":"1861","author":"Kang","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e129736","DOI":"10.1172\/jci.insight.129736","article-title":"OX40 expression in neutrophils promotes hepatic ischemia\/reperfusion injury","volume":"4","author":"Jin","year":"2019","journal-title":"JCI Insight"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/hep.24756","article-title":"Receptor activator of nuclear factor-\u03baB ligand (RANKL) protects against hepatic ischemia\/reperfusion injury in mice","volume":"55","author":"Sakai","year":"2012","journal-title":"Hepatology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41419-021-03493-2","article-title":"Hypothermic oxygenated perfusion inhibits HECTD3-mediated TRAF3 polyubiquitination to alleviate DCD liver ischemia-reperfusion injury","volume":"12","author":"Zhou","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41420-021-00784-7","article-title":"Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3\/CREB axis","volume":"8","author":"Wang","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jhep.2015.08.021","article-title":"Targeting TRAF3 signaling protects against hepatic ischemia\/reperfusions injury","volume":"64","author":"Hu","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.jss.2012.08.032","article-title":"RNA interference targeting RelB attenuates liver ischemia\/reperfusion injury","volume":"178","author":"Luo","year":"2012","journal-title":"J. Surg. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"19090","DOI":"10.1073\/pnas.1901056116","article-title":"Medullary thymic epithelial NF-kB-inducing kinase (NIK)\/IKK\u03b1 pathway shapes autoimmunity and liver and lung homeostasis in mice","volume":"116","author":"Shen","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.jhep.2017.02.025","article-title":"Thymic NF-\u03baB-inducing kinase regulates CD4(+) T cell-elicited liver injury and fibrosis in mice","volume":"67","author":"Shen","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrgastro.2015.35","article-title":"Alcoholic liver disease: Mechanisms of injury and targeted treatment","volume":"12","author":"Louvet","year":"2015","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/hep.1840060108","article-title":"CCl4-induced toxicity in isolated hepatocytes: The importance of direct solvent injury","volume":"6","author":"Berger","year":"1986","journal-title":"Hepatology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.fct.2013.11.006","article-title":"The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats","volume":"63","author":"Lee","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/hep.510310123","article-title":"Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice","volume":"31","author":"Kovalovich","year":"2000","journal-title":"Hepatology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/0016-5085(95)90149-3","article-title":"Prevention of carbon tetrachloride-induced rat liver injury by soluble tumor necrosis factor receptor","volume":"108","author":"Czaja","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/209036a0","article-title":"Necrogenic action of carbon tetrachloride in the rat: A speculative mechanism based on activation","volume":"209","author":"Slater","year":"1966","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0002-9440(10)65594-0","article-title":"Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride","volume":"153","author":"Shi","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1111\/j.1440-1746.2005.04065.x","article-title":"Lymphotoxin-beta production following bile duct ligation: Possible role for Kupffer cells","volume":"20","author":"Lee","year":"2005","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.tranon.2019.04.003","article-title":"Serum Levels of Hepatocyte Growth Factor and CD40 Ligand Predict Radiation-Induced Liver Injury","volume":"12","author":"Cuneo","year":"2019","journal-title":"Transl. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1016\/j.yexcr.2010.05.004","article-title":"Lipopolysaccharide-induced activation of NF-\u03baB non-canonical pathway requires BCL10 serine 138 and NIK phosphorylations","volume":"316","author":"Bhattacharyya","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1007\/s10753-020-01238-5","article-title":"Hepatoprotective Effect of Apigenin Against Liver Injury via the Non-canonical NF-\u03baB Pathway In Vivo and In Vitro","volume":"43","author":"Yue","year":"2020","journal-title":"Inflammation"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e22119","DOI":"10.1096\/fj.202101448R","article-title":"GBP5 promotes liver injury and inflammation by inducing hepatocyte apoptosis","volume":"36","author":"Ding","year":"2022","journal-title":"FASEB J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41575-020-0342-4","article-title":"Liver regeneration: Biological and pathological mechanisms and implications","volume":"18","author":"Michalopoulos","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chou, C.H., Ho, C.M., Lai, S.L., Chen, C.N., Wu, Y.M., Shun, C.T., Wen, W.F., and Lai, H.S. (2019). B-Cell Activating Factor Enhances Hepatocyte-Driven Angiogenesis via B-Cell CLL\/Lymphoma 10\/Nuclear Factor-KappaB Signaling during Liver Regeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205022"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.cyto.2012.05.029","article-title":"TNF-inducible expression of lymphotoxin-\u03b2 in hepatic cells: An essential role for NF-\u03baB and Ets1 transcription factors","volume":"60","author":"Subrata","year":"2012","journal-title":"Cytokine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.idc.2019.08.004","article-title":"Viral Hepatitis: Etiology, Epidemiology, Transmission, Diagnostics, Treatment, and Prevention","volume":"33","author":"Lanini","year":"2019","journal-title":"Infect Dis. Clin. N. Am."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1053\/j.gastro.2018.08.061","article-title":"Insights From Antiviral Therapy Into Immune Responses to Hepatitis B and C Virus Infection","volume":"156","author":"Rehermann","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.jcmgh.2015.09.004","article-title":"Natural Killer Cells in Viral Hepatitis","volume":"1","author":"Rehermann","year":"2015","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"730684","DOI":"10.3389\/fimmu.2021.730684","article-title":"Interplay Between Non-Canonical NF-\u03baB Signaling and Hepatitis B Virus Infection","volume":"12","author":"Lu","year":"2021","journal-title":"Front. Immunol"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature09907","article-title":"A diverse range of gene products are effectors of the type I interferon antiviral response","volume":"472","author":"Schoggins","year":"2011","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.cgh.2013.04.039","article-title":"Coffee reduces risk for hepatocellular carcinoma: An updated meta-analysis","volume":"11","author":"Bravi","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3349\/ymj.2020.61.6.460","article-title":"MicroRNA-98-5p Inhibits Tumorigenesis of Hepatitis B Virus-Related Hepatocellular Carcinoma by Targeting NF-\u03baB-Inducing Kinase","volume":"61","author":"Fei","year":"2020","journal-title":"Yonsei Med. J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1111\/j.1349-7006.2007.00591.x","article-title":"Interferon-gamma sensitizes hepatitis B virus-expressing hepatocarcinoma cells to 5-fluorouracil through inhibition of hepatitis B virus-mediated nuclear factor-kappaB activation","volume":"98","author":"Chung","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"S57","DOI":"10.1016\/j.ijsu.2016.05.050","article-title":"Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers","volume":"33","author":"Ruggiero","year":"2016","journal-title":"Int. J. Surg."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.biopha.2018.06.046","article-title":"Tauroursodeoxycholic acid alleviates hepatic ischemia reperfusion injury by suppressing the function of Kupffer cells in mice","volume":"106","author":"Xu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.ejps.2012.01.010","article-title":"Ferulic acid attenuates ischemia\/reperfusion-induced hepatocyte apoptosis via inhibition of JNK activation","volume":"45","author":"Kim","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ejphar.2012.09.009","article-title":"Lithium exacerbates hepatic ischemia\/reperfusion injury by inhibiting GSK-3\u03b2\/NF-\u03baB-mediated protective signaling in mice","volume":"697","author":"Xia","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"18017","DOI":"10.1038\/nrdp.2018.17","article-title":"Autoimmune hepatitis","volume":"4","author":"Vergani","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"S100","DOI":"10.1016\/j.jhep.2015.03.005","article-title":"Autoimmune hepatitis--Update 2015","volume":"62","author":"Manns","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1053\/j.gastro.2018.11.018","article-title":"Nuclear Translocation of RELB Is Increased in Diseased Human Liver and Promotes Ductular Reaction and Biliary Fibrosis in Mice","volume":"156","author":"Goeppert","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1590\/1414-431X20132665","article-title":"BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis","volume":"46","author":"Zhang","year":"2013","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7213","DOI":"10.1038\/s41467-021-27539-3","article-title":"The methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression","volume":"12","author":"Li","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ajpath.2021.09.005","article-title":"METTL3 Regulates Liver Homeostasis, Hepatocyte Ploidy, and Circadian Rhythm-Controlled Gene Expression in Mice","volume":"192","author":"Barajas","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"154702","DOI":"10.1016\/j.metabol.2021.154702","article-title":"METTL3 is required for maintaining \u03b2-cell function","volume":"116","author":"Li","year":"2021","journal-title":"Metab. Clin. Exp."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/s41467-020-15488-2","article-title":"METTL3 is essential for postnatal development of brown adipose tissue and energy expenditure in mice","volume":"11","author":"Wang","year":"2020","journal-title":"Nat. Commun."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/13\/4275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:42:12Z","timestamp":1760139732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/13\/4275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,2]]},"references-count":97,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["molecules27134275"],"URL":"https:\/\/doi.org\/10.3390\/molecules27134275","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,2]]}}}