{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:37:27Z","timestamp":1787060247344,"version":"build-2736575974"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2022JY9CPX"],"award-info":[{"award-number":["2022JY9CPX"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012032","name":"Fondazione Romeo ed Enrica Invernizzi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministry of Health","doi-asserted-by":"publisher","award":["RF-2021\\u201312372897"],"award-info":[{"award-number":["RF-2021\\u201312372897"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2022NH9MXB"],"award-info":[{"award-number":["2022NH9MXB"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["20229ZA2YF"],"award-info":[{"award-number":["20229ZA2YF"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.phrs.2025.107901","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T16:02:36Z","timestamp":1754582556000},"page":"107901","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Targeting of the IGFBP3\/TMEM219 pathway restores intestinal stem cells capability of healing mucosa in gastrointestinal autoimmune disorders"],"prefix":"10.1016","volume":"219","author":[{"given":"Giovanni","family":"Amabile","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"D\u2019Addio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Maestroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Zangarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Porzio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriella","family":"Camboni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Assi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Petrazzuolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Loretelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moufida","family":"Ben Nasr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Usuelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abdelsalam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy Joe","family":"Seelam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Zocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Corradi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virna","family":"Marin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Bruckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Nardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Canducci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Nardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Danese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianvincenzo","family":"Zuccotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca M.","family":"Sampietro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Ardizzone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fiorina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.phrs.2025.107901_bib1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s12079-013-0203-9","article-title":"Insulin-like growth factor binding protein-3 (IGFBP-3): novel ligands mediate unexpected functions","volume":"7","author":"Baxter","year":"2013","journal-title":"J. Cell Commun. Signal"},{"issue":"4-5","key":"10.1016\/j.phrs.2025.107901_bib2","first-page":"140","article-title":"Insulin-like growth factor binding proteins in the human circulation: a review","volume":"42","author":"Baxter","year":"1994","journal-title":"Horm. Res"},{"issue":"10","key":"10.1016\/j.phrs.2025.107901_bib3","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/nrd2359","article-title":"Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer","volume":"6","author":"Clemmons","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.phrs.2025.107901_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.mce.2020.111035","article-title":"Disorders of IGFs and IGF-1R signaling pathways","volume":"518","author":"Forbes","year":"2020","journal-title":"Mol. Cell Endocrinol."},{"issue":"5","key":"10.1016\/j.phrs.2025.107901_bib5","doi-asserted-by":"crossref","DOI":"10.3390\/cells9051261","article-title":"IGFBP-3\/IGFBP-3 receptor system as an Anti-Tumor and Anti-Metastatic signaling in cancer","volume":"9","author":"Cai","year":"2020","journal-title":"Cells"},{"issue":"39","key":"10.1016\/j.phrs.2025.107901_bib6","doi-asserted-by":"crossref","first-page":"30233","DOI":"10.1074\/jbc.M110.122226","article-title":"Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer","volume":"285","author":"Ingermann","year":"2010","journal-title":"J. Biol. Chem."},{"issue":"2-4","key":"10.1016\/j.phrs.2025.107901_bib7","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/0955-2235(95)00025-9","article-title":"Antiproliferative actions of insulin-like growth factor binding protein (IGFBP)-3 in human breast cancer cells","volume":"6","author":"Oh","year":"1995","journal-title":"Prog. Growth Factor Res"},{"issue":"20","key":"10.1016\/j.phrs.2025.107901_bib8","doi-asserted-by":"crossref","first-page":"17898","DOI":"10.1074\/jbc.M111.231035","article-title":"Insulin-like growth factor-binding protein-3 (IGFBP-3) blocks the effects of asthma by negatively regulating NF-kappaB signaling through IGFBP-3R-mediated activation of caspases","volume":"286","author":"Lee","year":"2011","journal-title":"J. Biol. Chem."},{"issue":"5","key":"10.1016\/j.phrs.2025.107901_bib9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1210\/er.2008-0028","article-title":"Unraveling insulin-like growth factor binding protein-3 actions in human disease","volume":"30","author":"Jogie-Brahim","year":"2009","journal-title":"Endocr. Rev."},{"issue":"5","key":"10.1016\/j.phrs.2025.107901_bib10","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1210\/en.2005-1270","article-title":"Insulin-like growth factor (IGF) binding protein-3 attenuates prostate tumor growth by IGF-dependent and IGF-independent mechanisms","volume":"147","author":"Silha","year":"2006","journal-title":"Endocrinology"},{"issue":"6","key":"10.1016\/j.phrs.2025.107901_bib11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0218091","article-title":"Blocking transmembrane219 protein signaling inhibits autophagy and restores normal cell death","volume":"14","author":"Joyce","year":"2019","journal-title":"PLoS One"},{"issue":"3","key":"10.1016\/j.phrs.2025.107901_bib12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1136\/mp.54.3.145","article-title":"Signalling pathways involved in antiproliferative effects of IGFBP-3: a review","volume":"54","author":"Baxter","year":"2001","journal-title":"Mol. Pathol."},{"issue":"7","key":"10.1016\/j.phrs.2025.107901_bib13","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.tem.2016.04.005","article-title":"Type 1 diabetes and dysfunctional intestinal homeostasis","volume":"27","author":"D'Addio","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"issue":"4","key":"10.1016\/j.phrs.2025.107901_bib14","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.stem.2015.07.010","article-title":"Circulating IGF-I and IGFBP3 levels control human colonic stem cell function and are disrupted in diabetic enteropathy","volume":"17","author":"D'Addio","year":"2015","journal-title":"Cell Stem Cell"},{"issue":"1","key":"10.1016\/j.phrs.2025.107901_bib15","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/s41467-022-28360-2","article-title":"The IGFBP3\/TMEM219 pathway regulates beta cell homeostasis","volume":"13","author":"D'Addio","year":"2022","journal-title":"Nat. Commun."},{"issue":"10","key":"10.1016\/j.phrs.2025.107901_bib16","article-title":"TMEM219 signaling promotes intestinal stem cell death and exacerbates colitis","volume":"135","author":"D'Addio","year":"2025","journal-title":"J. Clin. Invest"},{"issue":"5","key":"10.1016\/j.phrs.2025.107901_bib17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nri2761","article-title":"Therapeutic antibodies for autoimmunity and inflammation","volume":"10","author":"Chan","year":"2010","journal-title":"Nat. Rev. Immunol."},{"issue":"10","key":"10.1016\/j.phrs.2025.107901_bib18","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nrd3229","article-title":"Development trends for human monoclonal antibody therapeutics","volume":"9","author":"Nelson","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"issue":"5","key":"10.1016\/j.phrs.2025.107901_bib19","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.coph.2012.08.001","article-title":"Monoclonal antibody therapeutics: history and future","volume":"12","author":"Buss","year":"2012","journal-title":"Curr. Opin. Pharm."},{"issue":"9205","key":"10.1016\/j.phrs.2025.107901_bib20","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0140-6736(00)01034-5","article-title":"Therapeutic monoclonal antibodies","volume":"355","author":"Breedveld","year":"2000","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.phrs.2025.107901_bib21","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/d41573-019-00014-x","article-title":"2018 FDA drug approvals","volume":"18","author":"Mullard","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"issue":"1-2","key":"10.1016\/j.phrs.2025.107901_bib22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jim.2004.03.014","article-title":"J. Rapid generation of functional human IgG antibodies derived from Fab-on-phage display libraries","volume":"289","author":"Jostock","year":"2004","journal-title":"J. Immunol. Methods"},{"issue":"3","key":"10.1016\/j.phrs.2025.107901_bib23","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nbt0396-309","article-title":"Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library","volume":"14","author":"Vaughan","year":"1996","journal-title":"Nat. Biotechnol."},{"issue":"4","key":"10.1016\/j.phrs.2025.107901_bib24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.coi.2008.06.004","article-title":"Fully human antibodies from transgenic mouse and phage display platforms","volume":"20","author":"Lonberg","year":"2008","journal-title":"Curr. Opin. Immunol."},{"issue":"1","key":"10.1016\/j.phrs.2025.107901_bib25","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/ng0594-13","article-title":"Antigen-specific human monoclonal antibodies from mice engineered with human ig heavy and light chain YACs","volume":"7","author":"Green","year":"1994","journal-title":"Nat. Genet"},{"issue":"1","key":"10.1016\/j.phrs.2025.107901_bib26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrd.2016.230","article-title":"A comprehensive map of molecular drug targets","volume":"16","author":"Santos","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"issue":"5517","key":"10.1016\/j.phrs.2025.107901_bib27","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/256495a0","article-title":"Continuous cultures of fused cells secreting antibody of predefined specificity","volume":"256","author":"Kohler","year":"1975","journal-title":"Nature"},{"key":"10.1016\/j.phrs.2025.107901_bib28","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2022.962124","article-title":"In vivo phage display: a promising selection strategy for the improvement of antibody targeting and drug delivery properties","volume":"13","author":"Andre","year":"2022","journal-title":"Front Microbiol"},{"issue":"3","key":"10.1016\/j.phrs.2025.107901_bib29","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jmb.2004.04.062","article-title":"J. Camelized rabbit-derived VH single-domain intrabodies against vif strongly neutralize HIV-1 infectivity","volume":"340","author":"da Silva","year":"2004","journal-title":"J. Mol. Biol."},{"issue":"5","key":"10.1016\/j.phrs.2025.107901_bib30","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2165\/00063030-200822050-00003","article-title":"Recombinant antibodies as therapeutic agents: pathways for modeling new biodrugs","volume":"22","author":"Aires da Silva","year":"2008","journal-title":"BioDrugs"},{"issue":"6","key":"10.1016\/j.phrs.2025.107901_bib31","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/biot.201500458","article-title":"C JY. Advance in phage display technology for bioanalysis","volume":"11","author":"Tan","year":"2016","journal-title":"Biotechnol. J."},{"issue":"8","key":"10.1016\/j.phrs.2025.107901_bib32","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.biotechadv.2013.04.004","article-title":"In vivo phage display--a discovery tool in molecular biomedicine","volume":"31","author":"Babickova","year":"2013","journal-title":"Biotechnol. Adv."},{"issue":"4","key":"10.1016\/j.phrs.2025.107901_bib33","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/0022-2836(91)90354-9","article-title":"Multiple display of foreign peptides on a filamentous bacteriophage. Peptides from Plasmodium falciparum circumsporozoite protein as antigens","volume":"220","author":"Greenwood","year":"1991","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.phrs.2025.107901_bib34","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.3389\/fimmu.2020.01986","article-title":"Phage display derived monoclonal antibodies: from bench to bedside","volume":"11","author":"Alfaleh","year":"2020","journal-title":"Front Immunol."},{"issue":"7","key":"10.1016\/j.phrs.2025.107901_bib35","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/s41573-024-00953-0","article-title":"Navigating the complexities of drug development for inflammatory bowel disease","volume":"23","author":"Honap","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"issue":"10","key":"10.1016\/j.phrs.2025.107901_bib36","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/nm.2470","article-title":"Isolation and in vitro expansion of human colonic stem cells","volume":"17","author":"Jung","year":"2011","journal-title":"Nat. Med."},{"issue":"6137","key":"10.1016\/j.phrs.2025.107901_bib37","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1234852","article-title":"Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications","volume":"340","author":"Sato","year":"2013","journal-title":"Science"},{"issue":"6","key":"10.1016\/j.phrs.2025.107901_bib38","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"issue":"Pt 4","key":"10.1016\/j.phrs.2025.107901_bib39","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr D. Biol. Crystallogr"},{"issue":"9","key":"10.1016\/j.phrs.2025.107901_bib40","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1172\/JCI72189","article-title":"VEGF-C-dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease","volume":"124","author":"D'Alessio","year":"2014","journal-title":"J. Clin. Invest."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661825003263?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661825003263?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T10:37:05Z","timestamp":1778582225000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661825003263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":40,"alternative-id":["S1043661825003263"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2025.107901","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting of the IGFBP3\/TMEM219 pathway restores intestinal stem cells capability of healing mucosa in gastrointestinal autoimmune disorders","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2025.107901","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"107901"}}