{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:25Z","timestamp":1753891165970,"version":"3.41.2"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"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","doi-asserted-by":"publisher","award":["82270703, 82370423"],"award-info":[{"award-number":["82270703, 82370423"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2022JKXYD01001"],"award-info":[{"award-number":["2022JKXYD01001"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Metabolic dysfunction-associated steatohepatitis (MASH) is becoming increasingly prevalent. Regulated cell death (RCD) has emerged as a significant disease phenotype and may act as a marker for liver fibrosis. The present study aimed to investigate the regulation of RCD-related genes in MASH to elucidate the role of RCD in the progression of MASH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The gene expression profiles from the GSE130970 and GSE49541 datasets were retrieved from the Gene Expression Omnibus (GEO) database for analysis. A total of 101 combinations of 10 machine learning algorithms were employed to screen for characteristic RCD-related differentially expressed genes (DEGs) that reflect the progression of MASH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the enrichment pathways and functions of the feature genes. we performed cell classification analysis to investigate immune cell infiltration. Consensus cluster analysis was performed to identify MASH subtypes associated with RCD. The GSE89632 dataset was utilized to analyze the correlation of characteristic genes with clinical features of MASH. The DGIdb database was employed to screen for potential therapeutic drugs and compounds targeting the feature genes. In addition, we established mouse liver fibrosis models induced by methionine-choline-deficient (MCD) diet or CCl4 treatment, and further validated the expression of characteristic genes through quantitative real-time PCR (q-PCR). Lastly, we knocked down EPHA3 in LX2 cells to explore its effect on TGFb-induced activation of LX2 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study discovered a total of 11 RCD-associated DEGs, which predicted the progression of MASH. Advanced MASH has higher levels of immune cell infiltration and is significantly correlated with the RCD-related DEGs expression. MASH can be classified into two subtypes, cluster 1 and cluster 2, based on these feature genes. Compared with cluster 1, cluster 2 has highly expressed RCD-related DEGs, shows an increase in the degree of fibrosis. Furthermore, We discovered that the expression levels of feature genes were positively correlated with AST and ALT levels. Subsequently, We also evaluated the expression of these 11 feature genes in the liver tissues of mice with fibrosis induced by MCD or CCl4, and the results suggested that these genes may be involved in the development of fibrosis. WB results showed that the protein level of EPHA3 significantly increased in both mouse models of liver fibrosis. <jats:italic>In vitro<\/jats:italic>, we observed that knocking down EPHA3 in LX2 cells significantly inhibited the activation of the TGF-\u03b2\/Smad3 signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study sheds light on the fact that RCD contribute to the progression of MASH, high lighting potential therapeutic targets for treating this disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1542524","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T04:11:05Z","timestamp":1746677465000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of regulatory cell death-related genes during MASH progression using bioinformatics analysis and machine learning strategies"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhiqiang","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hangchi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruifen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youfei","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.jhep.2018.05.036","article-title":"Modeling nafld disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030","volume":"69","author":"Estes","year":"2018","journal-title":"J hepatology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A multisociety delphi consensus statement on new fatty liver disease nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J hepatology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nrgastro.2010.21","article-title":"Pathology of nonalcoholic fatty liver disease","volume":"7","author":"Brunt","year":"2010","journal-title":"Nat Rev Gastroenterology Hepatology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic steatohepatitis: A review","volume":"323","author":"Sheka","year":"2020","journal-title":"Jama"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.09.038","article-title":"Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: A prospective study","volume":"140","author":"Williams","year":"2011","journal-title":"Gastroenterology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0145-7","article-title":"From nash to hcc: current concepts and future challenges","volume":"16","author":"Anstee","year":"2019","journal-title":"Nat Rev Gastroenterology hepatology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/s41392-022-01110-y","article-title":"Regulated cell death (Rcd) in cancer: key pathways and targeted therapies","volume":"7","author":"Peng","year":"2022","journal-title":"Signal transduction targeted Ther"},{"key":"B8","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.108010","article-title":"Programming inflammatory cell death for therapy","volume":"232","author":"Christgen","year":"2022","journal-title":"Pharmacol Ther"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1053\/j.gastro.2012.06.036","article-title":"Deactivation of hepatic stellate cells during liver fibrosis resolution in mice","volume":"143","author":"Troeger","year":"2012","journal-title":"Gastroenterology"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101924R","article-title":"Dysregulation of the scribble\/yap\/\u03b2-catenin axis sustains the fibroinflammatory response in a pkhd1(-\/-) mouse model of congenital hepatic fibrosis","volume":"36","author":"Fabris","year":"2022","journal-title":"FASEB journal: Off Publ Fed Am Societies Exp Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/112_2018_10","article-title":"Targeting oxidative stress for the treatment of liver fibrosis","volume":"175","author":"Luangmonkong","year":"2018","journal-title":"Rev physiology Biochem Pharmacol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1115890","article-title":"Integrative network-based analysis on multiple gene expression omnibus datasets identifies novel immune molecular markers implicated in non-alcoholic steatohepatitis","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4383","DOI":"10.1038\/s41467-018-06318-7","article-title":"Single cell rna sequencing of human liver reveals distinct intrahepatic macrophage populations","volume":"9","author":"MacParland","year":"2018","journal-title":"Nat Commun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900752R","article-title":"Rip3 deficiency alleviates liver fibrosis by inhibiting rock1-tlr4-nf-\u03bab pathway in macrophages","volume":"33","author":"Wei","year":"2019","journal-title":"FASEB journal: Off Publ Fed Am Societies Exp Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601162","article-title":"Cutting edge: eosinophils undergo caspase-1-mediated pyroptosis in response to necrotic liver cells","volume":"199","author":"Palacios-Macapagal","year":"2017","journal-title":"J Immunol (Baltimore Md: 1950)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/comjnl\/bxaa191","article-title":"Computer-aided diagnosis system for chronic obstructive pulmonary disease using empirical wavelet transform on auscultation sounds","volume":"64","author":"G\u00f6k\u00e7en","year":"2019","journal-title":"Comput J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188774","article-title":"Mapk8 and capn1 as potential biomarkers of intervertebral disc degeneration overlapping immune infiltration, autophagy, and cerna","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1658","article-title":"Quantitative analysis of high-throughput biological data","volume-title":"WIREs Computational Molecular Science","author":"Juan","year":"2023"},{"key":"B20","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41698-024-00570-5","article-title":"Pan-cancer evaluation of regulated cell death to predict overall survival and immune checkpoint inhibitor response","volume":"8","author":"Zhang","year":"2024","journal-title":"NPJ Precis Oncol"},{"key":"B21","doi-asserted-by":"publisher","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 Gastroenterology hepatology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"16","DOI":"10.21037\/tgh.2019.09.08","article-title":"Epidemiology of non-alcoholic and alcoholic fatty liver diseases","volume":"5","author":"Mitra","year":"2020","journal-title":"Trans gastroenterology hepatology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27406","article-title":"The global burden of liver disease: the major impact of China","volume":"60","author":"Wang","year":"2014","journal-title":"Hepatology (Baltimore Md)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.003","article-title":"Genetics and epigenetics of nafld and nash: clinical impact","volume":"68","author":"Eslam","year":"2018","journal-title":"J hepatology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-326874","article-title":"Current therapies and new developments in nash","volume":"71","author":"Dufour","year":"2022","journal-title":"Gut"},{"key":"B26","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/s41420-023-01749-8","article-title":"Programmed cell death in hepatic fibrosis: current and perspectives","volume":"9","author":"Lu","year":"2023","journal-title":"Cell Death Discov"},{"key":"B27","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/s41419-021-03749-x","article-title":"Fas\/fasl mediates nf-\u03babp65\/puma-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis","volume":"12","author":"Tan","year":"2021","journal-title":"Cell Death Dis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/s41419-019-1954-x","article-title":"Il-6-driven fasl promotes nf-\u03babp65\/puma-mediated apoptosis in portal hypertensive gastropathy","volume":"10","author":"Tan","year":"2019","journal-title":"Cell Death Dis"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i25.2661","article-title":"Apoptosis and non-alcoholic fatty liver diseases","volume":"24","author":"Kanda","year":"2018","journal-title":"World J gastroenterology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s00018-022-04319-w","article-title":"Macrophages evoke autophagy of hepatic stellate cells to promote liver fibrosis in nafld mice via the pge2\/ep4 pathway","volume":"79","author":"Cao","year":"2022","journal-title":"Cell Mol Life sciences: CMLS"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.10.005","article-title":"Carvedilol attenuates liver fibrosis by suppressing autophagy and promoting apoptosis in hepatic stellate cells","volume":"108","author":"Meng","year":"2018","journal-title":"Biomedicine pharmacotherapy = Biomedecine pharmacotherapie"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.044","article-title":"Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues","volume":"142","author":"Hern\u00e1ndez-Gea","year":"2012","journal-title":"Gastroenterology"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.S317701","article-title":"Doxazosin attenuates liver fibrosis by inhibiting autophagy in hepatic stellate cells via activation of the pi3k\/akt\/mtor signaling pathway","volume":"15","author":"Xiu","year":"2021","journal-title":"Drug design Dev Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1055\/s-0035-1571272","article-title":"Targeting cell death and sterile inflammation loop for the treatment of nonalcoholic steatohepatitis","volume":"36","author":"Wree","year":"2016","journal-title":"Semin liver Dis"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.07.041","article-title":"Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis","volume":"74","author":"Gaul","year":"2021","journal-title":"J hepatology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.780496","article-title":"The nlrp3 inflammasome in non-alcoholic fatty liver disease and steatohepatitis: therapeutic targets and treatment","volume":"13","author":"Yu","year":"2022","journal-title":"Front Pharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00732-19","article-title":"Taurine alleviates schistosoma-induced liver injury by inhibiting the txnip\/nlrp3 inflammasome signal pathway and pyroptosis","volume":"87","author":"Liu","year":"2019","journal-title":"Infection Immun"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.04.009","article-title":"Caspase-11-mediated hepatocytic pyroptosis promotes the progression of nonalcoholic steatohepatitis","volume":"12","author":"Zhu","year":"2021","journal-title":"Cell Mol gastroenterology hepatology"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100695","article-title":"Tak1 deficiency promotes liver injury and tumorigenesis via ferroptosis and macrophage cgas-sting signalling","volume":"5","author":"Su","year":"2023","journal-title":"JHEP reports: Innovation hepatology"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102131","article-title":"Fibroblast growth factor 21 attenuates iron overload-induced liver injury and fibrosis by inhibiting ferroptosis","volume":"46","author":"Wu","year":"2021","journal-title":"Redox Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1071844","article-title":"Pharmacological modulation of ferroptosis as a therapeutic target for liver fibrosis","volume":"13","author":"Li","year":"2022","journal-title":"Front Pharmacol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated tca cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Sci (New York NY)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0291-9","article-title":"Mitochondrial metabolism promotes adaptation to proteotoxic stress","volume":"15","author":"Tsvetkov","year":"2019","journal-title":"Nat Chem Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.62347\/etjh6697","article-title":"The potential value of cuprotosis (Copper-induced cell death) in the therapy of clear cell renal cell carcinoma","volume":"12","author":"Qi","year":"2022","journal-title":"Am J Cancer Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.metabol.2019.153947","article-title":"Akr1d1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease","volume":"99","author":"Nikolaou","year":"2019","journal-title":"Metabolism: Clin Exp"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0164-5","article-title":"The molecular machinery of regulated cell death","volume":"29","author":"Tang","year":"2019","journal-title":"Cell Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00675-6","article-title":"Macrophage functional diversity in nafld - more than inflammation","volume":"18","author":"Barreby","year":"2022","journal-title":"Nat Rev Endocrinol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00639-3","article-title":"Immune cell-mediated features of non-alcoholic steatohepatitis","volume":"22","author":"Huby","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.760860","article-title":"Emerging roles of T cells in the pathogenesis of nonalcoholic steatohepatitis and hepatocellular carcinoma","volume":"12","author":"Hirsova","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13839","article-title":"The microbiota maintain homeostasis of liver-resident \u0393\u03b4t-17 cells in a lipid antigen\/cd1d-dependent manner","volume":"7","author":"Li","year":"2017","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00056.2013","article-title":"Involvement of mast cells in adipose tissue fibrosis","volume":"306","author":"Hirai","year":"2014","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.11.029","article-title":"Hepatic mast cell concentration directly correlates to stage of fibrosis in nash","volume":"86","author":"Lombardo","year":"2019","journal-title":"Hum Pathol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e84916","DOI":"10.1172\/jci.insight.84916","article-title":"Tubular dickkopf-3 promotes the development of renal atrophy and fibrosis","volume":"1","author":"Federico","year":"2016","journal-title":"JCI insight"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2006.2001.543250","DOI":"10.1101\/2023.06.01.543250%JbioRxiv","article-title":"Thrombospondin 2 is a key determinant of fibrogenesis in nafld","volume":"2023","author":"Kimura","year":"2023","journal-title":"bioRxiv"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31995","article-title":"Transcriptomics identify thrombospondin-2 as a biomarker for nash and advanced liver fibrosis","volume":"74","author":"Kozumi","year":"2021","journal-title":"Hepatology (Baltimore Md)"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.035","article-title":"S100a4 promotes liver fibrosis via activation of hepatic stellate cells","volume":"62","author":"Chen","year":"2015","journal-title":"J hepatology"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01319-7","article-title":"Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach","volume":"56","author":"Kwon","year":"2024","journal-title":"Exp Mol Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0219764","article-title":"Aebp1 expression increases with severity of fibrosis in nash and is regulated by glucose, palmitate, and mir-372-3p","volume":"14","author":"Gerhard","year":"2019","journal-title":"PloS One"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.08.366","article-title":"86p the predictive values of epha3 mutations for response to immune checkpoint inhibitors in solid tumors","volume":"32","author":"Bing","year":"2021","journal-title":"Ann Oncol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.141061","article-title":"Antibody-mediated depletion of ccr10+Epha3+ Cells ameliorates fibrosis in ipf","volume":"6","author":"Hohmann","year":"2021","journal-title":"JCI Insight"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noz175.022%JNeuro-Oncology","article-title":"Atim-23. Preliminary findings of a phase I safety and bioimaging trial of kb004 (Ifabotuzumab) in patients with glioblastoma","volume":"21","author":"Gan","year":"2019","journal-title":"Neuro-Oncology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/s41584-021-00683-2","article-title":"Advances in epigenetics in systemic sclerosis: molecular mechanisms and therapeutic potential","volume":"17","author":"Tsou","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32299","article-title":"A strategy of vascular-targeted therapy for liver fibrosis","volume":"76","author":"Lin","year":"2022","journal-title":"Hepatology (Baltimore Md)"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.11.007","article-title":"A microrna-29 mimic (Remlarsen) represses extracellular matrix expression and fibroplasia in the skin","volume":"139","author":"Gallant-Behm","year":"2019","journal-title":"J Invest Dermatol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1172\/jci153110","article-title":"Carbonic anhydrase xii mediates the survival and prometastatic functions of macrophages in human hepatocellular carcinoma","volume":"132","author":"Ning","year":"2022","journal-title":"J Clin Invest"},{"key":"B66","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1053\/j.gastro.2021.02.051","article-title":"Squalene epoxidase induces nonalcoholic steatohepatitis via binding to carbonic anhydrase iii and is a therapeutic target","volume":"160","author":"Liu","year":"2021","journal-title":"Gastroenterology"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1542524\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T04:11:07Z","timestamp":1746677467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1542524\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,8]]},"references-count":66,"alternative-id":["10.3389\/fimmu.2025.1542524"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1542524","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2025,5,8]]},"article-number":"1542524"}}