{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T12:55:42Z","timestamp":1793019342177,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.bbadis.2025.168140","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:07:25Z","timestamp":1766048845000},"page":"168140","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["HKDC1 promotes the H3K18 lactylation of the promoter of ORMDL3 to induce the activation of hepatic stellate cells in liver cirrhosis"],"prefix":"10.1016","volume":"1872","author":[{"given":"Yanan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaiqin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexue","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbadis.2025.168140_bb0005","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S2468-1253(19)30349-8","article-title":"The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the global burden of disease study 2017","volume":"5","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0010","first-page":"759","article-title":"Cirrhosis: diagnosis and management","volume":"100","author":"Smith","year":"2019","journal-title":"Am. Fam. Physician"},{"key":"10.1016\/j.bbadis.2025.168140_bb0015","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.intimp.2023.111002","article-title":"HSC-derived exosomal miR-199a-5p promotes HSC activation and hepatocyte EMT via targeting SIRT1 in hepatic fibrosis","volume":"124","author":"Lu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0020","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1111\/j.1440-1746.2006.04658.x","article-title":"Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis","volume":"22","author":"Kisseleva","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0025","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.addr.2017.05.007","article-title":"Hepatic stellate cells as key target in liver fibrosis","volume":"121","author":"Higashi","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.bbadis.2025.168140_bb0030","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/cdd.2012.100","article-title":"Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation","volume":"20","author":"Dichtel-Danjoy","year":"2013","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.bbadis.2025.168140_bb0035","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0040","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.cbd.2007.11.002","article-title":"Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene","volume":"3","author":"Irwin","year":"2008","journal-title":"Comp. Biochem. Physiol. Part D Genomics Proteomics"},{"key":"10.1016\/j.bbadis.2025.168140_bb0045","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1369\/0022155418756849","article-title":"Studies on the Tissue Localization of HKDC1, a Putative Novel Fifth Hexokinase, in Humans","volume":"66","author":"Khan","year":"2018","journal-title":"J. Histochem. Cytochem."},{"key":"10.1016\/j.bbadis.2025.168140_bb0050","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1210\/en.2016-1288","article-title":"HKDC1 is a novel hexokinase involved in whole-body glucose use","volume":"157","author":"Ludvik","year":"2016","journal-title":"Endocrinology"},{"key":"10.1016\/j.bbadis.2025.168140_bb0055","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.tem.2021.10.006","article-title":"Hexokinase domain-containing protein-1 in metabolic diseases and beyond","volume":"33","author":"Zapater","year":"2022","journal-title":"Trends Endocrinol. Metab."},{"key":"10.1016\/j.bbadis.2025.168140_bb0060","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.canlet.2023.216305","article-title":"HKDC1 reprograms lipid metabolism to enhance gastric cancer metastasis and cisplatin resistance via forming a ribonucleoprotein complex","volume":"569","author":"Zhao","year":"2023","journal-title":"Cancer Lett."},{"key":"10.1016\/j.bbadis.2025.168140_bb0065","doi-asserted-by":"crossref","first-page":"020","DOI":"10.1186\/s12935-020-01539-7","article-title":"HKDC1 promotes the tumorigenesis and glycolysis in lung adenocarcinoma via regulating AMPK\/mTOR signaling pathway","volume":"20","author":"Wang","year":"2020","journal-title":"Cancer Cell Int."},{"key":"10.1016\/j.bbadis.2025.168140_bb0070","first-page":"024","article-title":"HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bbadis.2025.168140_bb0075","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1210\/en.2018-00887","article-title":"Hepatic HKDC1 expression contributes to liver metabolism","volume":"160","author":"Pusec","year":"2019","journal-title":"Endocrinology"},{"key":"10.1016\/j.bbadis.2025.168140_bb0080","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.jhep.2015.07.033","article-title":"Activation of Slit2-Robo1 signaling promotes liver fibrosis","volume":"63","author":"Chang","year":"2015","journal-title":"J. Hepatol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0085","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s12951-023-01942-y","article-title":"Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP\/LOXL2 pathway","volume":"21","author":"Cheng","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0090","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202201182RR","article-title":"LincRNA-ROR\/miR-145\/ZEB2 regulates liver fibrosis by modulating HERC5-mediated p53 ISGylation","volume":"37","author":"Shen","year":"2023","journal-title":"FASEB J."},{"key":"10.1016\/j.bbadis.2025.168140_bb0095","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bbadis.2025.168140_bb0100","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.metabol.2016.01.010","article-title":"Nonalcoholic fatty liver disease and hepatocellular carcinoma","volume":"65","author":"Zoller","year":"2016","journal-title":"Metabolism"},{"key":"10.1016\/j.bbadis.2025.168140_bb0105","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/hep.27332","article-title":"Hepatic inflammation and fibrosis: functional links and key pathways","volume":"61","author":"Seki","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2025.168140_bb0110","doi-asserted-by":"crossref","first-page":"023","DOI":"10.1038\/s41598-023-33924-3","article-title":"Liver-specific overexpression of HKDC1 increases hepatocyte size and proliferative capacity","volume":"13","author":"Pusec","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bbadis.2025.168140_bb0115","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.bbrc.2016.05.007","article-title":"High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma","volume":"474","author":"Zhang","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.bbadis.2025.168140_bb0120","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrgastro.2016.97","article-title":"Liver regeneration - mechanisms and models to clinical application","volume":"13","author":"Forbes","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0125","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev-immunol-051116-052415","article-title":"Immune responses in the liver","volume":"36","author":"Kubes","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0130","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1172\/JCI66369","article-title":"Hepatic stellate cells in liver development, regeneration, and cancer","volume":"123","author":"Yin","year":"2013","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bbadis.2025.168140_bb0135","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","article-title":"Liver fibrosis: pathophysiology, pathogenetic targets and clinical issues","volume":"65","author":"Parola","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"10.1016\/j.bbadis.2025.168140_bb0140","doi-asserted-by":"crossref","first-page":"022","DOI":"10.1038\/s41598-022-14285-9","article-title":"Analysis of hepatic fibrosis markers in the serum of chronic hepatitis B patients according to basal core promoter\/precore mutants","volume":"12","author":"Lefeuvre","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bbadis.2025.168140_bb0145","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.matbio.2015.03.005","article-title":"The role of TIMPs in regulation of extracellular matrix proteolysis","volume":"44-46","author":"Arpino","year":"2015","journal-title":"Matrix Biol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0150","article-title":"Correlation of serum M-CSF, CER, and TIMP-1 levels with liver fibrosis in viral hepatitis","volume":"30","author":"Yao","year":"2022","journal-title":"Comput. Math. Methods Med."},{"key":"10.1016\/j.bbadis.2025.168140_bb0155","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cmet.2020.10.026","article-title":"The power of plasticity-metabolic regulation of hepatic stellate cells","volume":"33","author":"Trivedi","year":"2021","journal-title":"Cell Metab."},{"key":"10.1016\/j.bbadis.2025.168140_bb0160","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1111\/j.1440-1746.2006.04584.x","article-title":"Hepatic stellate cells and the reversal of fibrosis","volume":"21","author":"Kisseleva","year":"2006","journal-title":"J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0165","doi-asserted-by":"crossref","first-page":"207","DOI":"10.14218\/JCTH.2021.00101","article-title":"KRT17 promotes the activation of HSCs via EMT in liver fibrosis","volume":"10","author":"Chen","year":"2022","journal-title":"J. Clin. Transl. Hepatol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0170","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1097\/HEP.0000000000000569","article-title":"Canonical Wnt signaling promotes HSC glycolysis and liver fibrosis through an LDH-A\/HIF-1\u03b1 transcriptional complex","volume":"79","author":"Wang","year":"2024","journal-title":"Hepatology"},{"key":"10.1016\/j.bbadis.2025.168140_bb0175","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1053\/j.gastro.2020.03.008","article-title":"CPEB4 increases expression of PFKFB3 to induce glycolysis and activate mouse and human hepatic stellate cells, promoting liver fibrosis","volume":"159","author":"Mejias","year":"2020","journal-title":"Gastroenterology"},{"key":"10.1016\/j.bbadis.2025.168140_bb0180","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41401-021-00658-9","article-title":"Bmal1 inhibits phenotypic transformation of hepatic stellate cells in liver fibrosis via IDH1\/\u03b1-KG-mediated glycolysis","volume":"43","author":"Xu","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.bbadis.2025.168140_bb0185","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3748\/wjg.v28.i1.123","article-title":"Focal adhesion kinase-related non-kinase ameliorates liver fibrosis by inhibiting aerobic glycolysis via the FAK\/Ras\/c-myc\/ENO1 pathway","volume":"28","author":"Huang","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0190","article-title":"HKDC1 silencing inhibits proliferation and glycolysis of gastric cancer cells","volume":"2023","author":"Yu","year":"2023"},{"key":"10.1016\/j.bbadis.2025.168140_bb0195","doi-asserted-by":"crossref","DOI":"10.1186\/s12935-020-01539-7","article-title":"Hkdc1 promotes the tumorigenesis and glycolysis in lung adenocarcinoma via regulating AMPK\/mTOR signaling pathway","volume":"20","author":"Wang","year":"2020","journal-title":"Cancer Cell Int."},{"key":"10.1016\/j.bbadis.2025.168140_bb0200","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-cellbio-092910-154237","article-title":"Aerobic glycolysis: meeting the metabolic requirements of cell proliferation","volume":"27","author":"Lunt","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0205","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ai.2017.06.001","article-title":"Chromosome 17q21 genes ORMDL3 and GSDMB in asthma and immune diseases","volume":"135","author":"Das","year":"2017","journal-title":"Adv. Immunol."},{"key":"10.1016\/j.bbadis.2025.168140_bb0210","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.bbadis.2025.168140_bb0215","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s12974-023-02879-7","article-title":"H3K18 lactylation of senescent microglia potentiates brain aging and Alzheimer\u2019s disease through the NF\u03baB signaling pathway","volume":"20","author":"Wei","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.bbadis.2025.168140_bb0220","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1080\/15548627.2023.2249762","article-title":"Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer","volume":"20","author":"Li","year":"2024","journal-title":"Autophagy"}],"container-title":["Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0925443925004909?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0925443925004909?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:26:18Z","timestamp":1769505978000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0925443925004909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S0925443925004909"],"URL":"https:\/\/doi.org\/10.1016\/j.bbadis.2025.168140","relation":{},"ISSN":["0925-4439"],"issn-type":[{"value":"0925-4439","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"HKDC1 promotes the H3K18 lactylation of the promoter of ORMDL3 to induce the activation of hepatic stellate cells in liver cirrhosis","name":"articletitle","label":"Article Title"},{"value":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbadis.2025.168140","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"168140"}}