{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:01:33Z","timestamp":1790226093812,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Progressive familial intrahepatic cholestasis type 3 (PFIC3), caused by MDR3 deficiency (MDR2 in mice), is a lethal pediatric liver disease characterized by early-onset persistent cholestasis, progressive fibrosis, cirrhosis, and eventual liver failure. MDR3 is a phosphatidylcholine transporter located in the canalicular membrane of hepatocytes, and its deficiency leads to the accumulation of free bile acids, which damage epithelial cells due to their detergent-like effect. Therapeutic options remain limited, highlighting the need to identify molecular drivers of disease progression and novel pharmacological strategies. To investigate the molecular alterations associated with this deficiency, our laboratory performed functional proteomic analyses in patient samples and murine hepatic organoids, revealing consistent reprogramming of one-carbon metabolism (OCM). Based on these findings, we explored the therapeutic potential and molecular mechanisms of 5\u2032-methylthioadenosine (MTA), a metabolite involved in this pathway. Using hepatocellular carcinoma cells (PLCs), we combined quantitative shotgun proteomics with the proteome integral solubility alteration (PISA) assay to characterize functional responses and identify direct protein targets of MTA. To reinforce the physiological relevance of our findings, we extended the PISA analysis to liver protein extracts from the Mdr2\u2212\/\u2212 mouse model of chronic cholestatic injury, enabling validation of candidate target interactions observed in cellular extracts. Proteomic profiling revealed that MTA induces significant alterations in cell division processes, epigenetic regulatory networks, and energy metabolism, thereby promoting an adaptive phenotype characterized by metabolic plasticity, microenvironmental reorganization, and immunomodulation. These findings provide a robust molecular framework for understanding the hepatic response to MTA and shed new light on the mechanisms that may underlie its beneficial effects. In addition, they provide a valuable platform for further investigation of the therapeutic potential of this compound and its prospective translation into clinical practice.<\/jats:p>","DOI":"10.3390\/cells15191720","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:17:54Z","timestamp":1790065074000},"page":"1720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding the Cellular Response to Methylthioadenosine Uncovers Novel Targets for Chronic Liver Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Irene","family":"Bl\u00e1zquez-Garc\u00eda","sequence":"first","affiliation":[{"name":"Functional Proteomics Laboratory, National Center for Biotechnology (CNB-CSIC), Darwin 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-8449","authenticated-orcid":false,"given":"Laura","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, National Center for Biotechnology (CNB-CSIC), Darwin 3, 28049 Madrid, Spain"},{"name":"Leukemia Therapy Resistance Lab, Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5963-6500","authenticated-orcid":false,"given":"Mary Dayne S.","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Macromolecular Structure, National Center for Biotechnology (CNB-CSIC), Darwin 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9rico","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, National Center for Biotechnology (CNB-CSIC), Darwin 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Cuervo","sequence":"additional","affiliation":[{"name":"Department of Macromolecular Structure, National Center for Biotechnology (CNB-CSIC), Darwin 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6837-7056","authenticated-orcid":false,"given":"Alberto","family":"Paradela","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, National Center for Biotechnology (CNB-CSIC), Darwin 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0231-5159","authenticated-orcid":false,"given":"Fernando J.","family":"Corrales","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, National Center for Biotechnology (CNB-CSIC), Darwin 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jhep.2018.09.014","article-title":"Burden of liver diseases in the world","volume":"70","author":"Asrani","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.jhep.2018.05.011","article-title":"Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies","volume":"69","author":"Pimpin","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1056\/NEJMra2412865","article-title":"Metabolic Dysfunction-Associated Steatotic Liver Disease","volume":"393","author":"Targher","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/hep.31288","article-title":"Epidemiology of Hepatocellular Carcinoma","volume":"73","author":"McGlynn","year":"2021","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"goaf088","DOI":"10.1093\/gastro\/goaf088","article-title":"Alcohol-related liver disease","volume":"13","author":"Herms","year":"2025","journal-title":"Gastroenterol. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1056\/NEJMra1810477","article-title":"Global Elimination of Chronic Hepatitis","volume":"380","author":"Thomas","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1053\/j.gastro.2010.09.004","article-title":"Pathogenesis of cholestatic liver disease and therapeutic approaches","volume":"139","author":"Hirschfield","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1007\/s10620-025-09431-y","article-title":"Advancing the Diagnosis and Management of Genetic Cholestatic Liver Disease in Adults","volume":"71","author":"Nasir","year":"2026","journal-title":"Dig. Dis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"98","DOI":"10.4254\/wjh.v14.i1.98","article-title":"Recent updates on progressive familial intrahepatic cholestasis types 1, 2 and 3: Outcome and therapeutic strategies","volume":"14","author":"Alam","year":"2022","journal-title":"World J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2106702118","DOI":"10.1073\/pnas.2106702118","article-title":"Structures of ABCB4 provide insight into phosphatidylcholine translocation","volume":"118","author":"Nosol","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.str.2021.05.013","article-title":"Evidence for a credit-card-swipe mechanism in the human PC floppase ABCB4","volume":"29","author":"Prescher","year":"2021","journal-title":"Structure"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"278","DOI":"10.5500\/wjt.v6.i2.278","article-title":"Liver transplantation and the management of progressive familial intrahepatic cholestasis in children","volume":"6","author":"Mehl","year":"2016","journal-title":"World J. Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cld.2018.06.003","article-title":"Progressive Familial Intrahepatic Cholestasis","volume":"22","author":"Bull","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7470","DOI":"10.3748\/wjg.v26.i47.7470","article-title":"Molecular overview of progressive familial intrahepatic cholestasis","volume":"26","author":"Amirneni","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/biof.2041","article-title":"Molecular basis of progressive familial intrahepatic cholestasis 3. A proteomics study","volume":"50","author":"Guerrero","year":"2024","journal-title":"Biofactors"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Guerrero, L., Vindel-Alfageme, J., Hierro, L., Stark, L., Vicent, D., Sorzano, C.O.S., and Corrales, F.J. (2024). Discrimination of Etiologically Different Cholestasis by Modeling Proteomics Datasets. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073684"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.mam.2016.11.007","article-title":"One-carbon metabolism and epigenetics","volume":"54","author":"Friso","year":"2017","journal-title":"Mol. Asp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.tibs.2024.12.009","article-title":"Mechanisms and rationales of SAM homeostasis","volume":"50","author":"Xing","year":"2025","journal-title":"Trends Biochem. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1080\/14789450.2018.1521277","article-title":"Liver cancer-associated changes to the proteome: What deserves clinical focus?","volume":"15","author":"Mato","year":"2018","journal-title":"Expert Rev. Proteom."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Guerrero, L., Paradela, A., and Corrales, F.J. (2022). Targeted Proteomics for Monitoring One-Carbon Metabolism in Liver Diseases. Metabolites, 12.","DOI":"10.3390\/metabo12090779"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0168-8278(00)00078-7","article-title":"5\u2032-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication","volume":"34","author":"Simile","year":"2001","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"G71","DOI":"10.1152\/ajpgi.00549.2011","article-title":"Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice","volume":"303","author":"Benight","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1002\/hep.1840160427","article-title":"S-adenosylmethionine treatment prevents carbon tetrachloride\u2014Induced S-adenosylmethionine synthetase inactivation and attenuates liver injury","volume":"16","author":"Corrales","year":"1992","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/S0168-8278(99)80263-3","article-title":"S-adenosylmethionine in alcoholic liver cirrhosis: A randomized, placebo-controlled, double-blind, multicenter clinical trial","volume":"30","author":"Mato","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/j.biocel.2003.11.016","article-title":"Methylthioadenosine","volume":"36","author":"Avila","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/ana.20895","article-title":"Methylthioadenosine reverses brain autoimmune disease","volume":"60","author":"Moreno","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1002\/hep.20154","article-title":"5\u2032-Methylthioadenosine Modulates the Inflammatory Response to Endotoxin in Mice and in Rat Hepatocytes","volume":"39","author":"Hevia","year":"2004","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Latasa, M.U., Gil-Puig, C., Fern\u00e1ndez-Barrena, M.G., Rodr\u00edguez-Ortigosa, C.M., Banales, J.M., Urtasun, R., Go\u00f1i, S., M\u00e9ndez, M., Arcelus, S., and Juanarena, N. (2010). Oral Methylthioadenosine Administration Attenuates Fibrosis and Chronic Liver Disease Progression in Mdr2-\/- Mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015690"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e4556","DOI":"10.21769\/BioProtoc.4556","article-title":"Proteome Integral Solubility Alteration (PISA) Assay in Mammalian Cells for Deep, High-Confidence, and High-Throughput Target Deconvolution","volume":"12","author":"Zhang","year":"2022","journal-title":"Bio Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125988","DOI":"10.1016\/j.talanta.2024.125988","article-title":"Refinement of paramagnetic bead-based digestion protocol for automatic sample preparation using an artificial neural network","volume":"274","author":"Ciordia","year":"2024","journal-title":"Talanta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11229","DOI":"10.1073\/pnas.1902639116","article-title":"Structure of full-length human phenylalanine hydroxylase in complex with tetrahydrobiopterin","volume":"116","author":"Flydal","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1021\/acs.jproteome.9b00500","article-title":"Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution","volume":"18","author":"Gaetani","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e9232","DOI":"10.15252\/msb.20199232","article-title":"Thermal proteome profiling for interrogating protein interactions","volume":"16","author":"Mateus","year":"2020","journal-title":"Mol. Syst. Biol."},{"key":"ref_35","first-page":"759","article-title":"Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy","volume":"48","author":"Pegg","year":"1988","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0741-8329(02)00227-6","article-title":"Chemoprevention of hepatocarcinogenesis: S-adenosyl-L-methionine","volume":"27","author":"Pascale","year":"2002","journal-title":"Alcohol"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0006-291X(81)80208-2","article-title":"Inactivation of S-adenosylhomocysteine hydrolase by 5\u2032-deoxy-5\u2032-methylthioadenosine","volume":"100","author":"Ferro","year":"1981","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7573","DOI":"10.1021\/bi0160720","article-title":"L-phenylalanine binding and domain organization in human phenylalanine hydroxylase: A differential scanning calorimetry study","volume":"41","author":"Thorolfsson","year":"2002","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e132305","DOI":"10.1172\/JCI132305","article-title":"Bile acid-activated macrophages promote biliary epithelial cell proliferation through integrin alphavbeta6 upregulation following liver injury","volume":"131","author":"Guillot","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1665-2681(19)31355-9","article-title":"S-adenosylmethionine metabolism and liver disease","volume":"12","author":"Mato","year":"2013","journal-title":"Ann. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1152\/physrev.00047.2011","article-title":"S-adenosylmethionine in liver health, injury, and cancer","volume":"92","author":"Lu","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1111\/j.1440-1746.2007.05289.x","article-title":"S-Adenosylmethionine in cell growth, apoptosis and liver cancer","volume":"23","author":"Lu","year":"2008","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_43","first-page":"267","article-title":"Influence of impaired liver methionine metabolism on the development of vascular disease and inflammation","volume":"3","author":"Avila","year":"2005","journal-title":"Curr. Med. Chem. Cardiovasc. Hematol. Agents"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1126\/science.aad5214","article-title":"MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells","volume":"351","author":"Kryukov","year":"2016","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1074\/mcp.M115.055772","article-title":"Methylthioadenosine (MTA) regulates liver cells proteome and methylproteome: Implications in liver biology and disease","volume":"15","author":"Bigaud","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e70033","DOI":"10.1002\/jimd.70033","article-title":"Adenosine Kinase: An Epigenetic Modulator and Drug Target","volume":"48","author":"Boison","year":"2025","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1128\/MCB.15.5.2800","article-title":"In vivo and in vitro arginine methylation of RNA-binding proteins","volume":"15","author":"Liu","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1038\/s41467-023-38863-1","article-title":"Decoding protein methylation function with thermal stability analysis","volume":"14","author":"Sayago","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1021\/acsptsci.4c00278","article-title":"The Ubiquitin Tale: Current Strategies and Future Challenges","volume":"7","author":"Upadhyay","year":"2024","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.jhep.2015.06.015","article-title":"Structural and functional hepatocyte polarity and liver disease","volume":"63","author":"Gissen","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1007\/s10753-014-9861-x","article-title":"5\u2032-Methylthioadenosine attenuates ischemia reperfusion injury after liver transplantation in rats","volume":"37","author":"Tang","year":"2014","journal-title":"Inflammation"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5188","DOI":"10.1111\/jcmm.13822","article-title":"The roles of TNFAIP2 in cancers and infectious diseases","volume":"22","author":"Jia","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/imm.13310","article-title":"IL-36 cytokines and gut immunity","volume":"163","author":"Ngo","year":"2021","journal-title":"Immunology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1034\/j.1600-065X.2000.17812.x","article-title":"Of genes and phenotypes: The immunological and molecular spectrum of combined immune deficiency. Defects of the gamma(c)-JAK3 signaling pathway as a model","volume":"178","author":"Notarangelo","year":"2000","journal-title":"Immunol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.3748\/wjg.v12.i11.1681","article-title":"Interleukin-10 and chronic liver disease","volume":"12","author":"Zhang","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.ajpath.2020.02.013","article-title":"Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor Deficiency Promotes the Ductular Reaction, Macrophage Accumulation, and Hepatic Fibrosis in the Abcb4(-\/-) Mouse","volume":"190","author":"Krishnan","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1053\/j.gastro.2004.11.006","article-title":"Amphiregulin: An early trigger of liver regeneration in mice","volume":"128","author":"Berasain","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/hep.30348","article-title":"The Epidermal Growth Factor Receptor Ligand Amphiregulin Protects From Cholestatic Liver Injury and Regulates Bile Acids Synthesis","volume":"69","author":"Santamaria","year":"2019","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"41991","DOI":"10.1074\/jbc.M112.356824","article-title":"Amphiregulin, an epidermal growth factor receptor ligand, plays an essential role in the pathogenesis of transforming growth factor-beta-induced pulmonary fibrosis","volume":"287","author":"Zhou","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.devcel.2005.12.011","article-title":"Stonin 2 is an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization and recycling","volume":"10","author":"Diril","year":"2006","journal-title":"Dev. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.semcdb.2014.01.005","article-title":"Amphiregulin","volume":"28","author":"Berasain","year":"2014","journal-title":"Semin. Cell Dev. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1720\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:23:27Z","timestamp":1790223807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1720"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":61,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cells15191720"],"URL":"https:\/\/doi.org\/10.3390\/cells15191720","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]}}}