{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T21:05:43Z","timestamp":1775768743201,"version":"3.50.1"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004374","name":"Chongqing Medical University","doi-asserted-by":"publisher","award":["CHCMU-2024-XKDF-1002"],"award-info":[{"award-number":["CHCMU-2024-XKDF-1002"]}],"id":[{"id":"10.13039\/501100004374","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272399"],"award-info":[{"award-number":["82272399"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.intimp.2025.115043","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T05:16:21Z","timestamp":1749446181000},"page":"115043","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Activin A exacerbates neonatal necrotizing enterocolitis via ALK4-mediated apoptosis and barrier disruption"],"prefix":"10.1016","volume":"161","author":[{"given":"Wenjing","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dapeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixin","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"9543","key":"10.1016\/j.intimp.2025.115043_bb0005","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/S0140-6736(06)69525-1","article-title":"Necrotising enterocolitis","volume":"368","author":"Lin","year":"2006","journal-title":"Lancet"},{"issue":"8","key":"10.1016\/j.intimp.2025.115043_bb0010","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jfma.2013.03.010","article-title":"Prevention of necrotizing enterocolitis in preterm very low birth weight infants: is it feasible?","volume":"113","author":"Lin","year":"2014","journal-title":"J. Formos. Med. Assoc."},{"issue":"1","key":"10.1016\/j.intimp.2025.115043_bb0015","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1186\/s12887-020-02231-5","article-title":"Global incidence of necrotizing enterocolitis: a systematic review and Meta-analysis","volume":"20","author":"Alsaied","year":"2020","journal-title":"BMC Pediatr."},{"issue":"11","key":"10.1016\/j.intimp.2025.115043_bb0020","doi-asserted-by":"crossref","first-page":"6043","DOI":"10.1073\/pnas.97.11.6043","article-title":"Inflammation in the developing human intestine: a possible pathophysiologic contribution to necrotizing enterocolitis","volume":"97","author":"Nanthakumar","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"7","key":"10.1016\/j.intimp.2025.115043_bb0025","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/s41575-022-00594-x","article-title":"Bench to bedside - new insights into the pathogenesis of necrotizing enterocolitis","volume":"19","author":"Hackam","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"1\u20132","key":"10.1016\/j.intimp.2025.115043_bb0030","article-title":"The role of intestinal epithelial barrier function in the development of NEC","volume":"3","author":"Halpern","year":"2015","journal-title":"Tissue Barriers"},{"issue":"3","key":"10.1016\/j.intimp.2025.115043_bb0035","first-page":"308","article-title":"Cell death of intestinal epithelial cells in intestinal diseases","volume":"72","author":"Subramanian","year":"2020","journal-title":"Sheng Li Xue Bao"},{"key":"10.1016\/j.intimp.2025.115043_bb0040","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.112709","article-title":"Pathological insights into activin a: molecular underpinnings and therapeutic prospects in various diseases","volume":"139","author":"Kundra","year":"2024","journal-title":"Int. Immunopharmacol."},{"issue":"7","key":"10.1016\/j.intimp.2025.115043_bb0045","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1093\/emboj\/cdg156","article-title":"Structures of an ActRIIB:activin a complex reveal a novel binding mode for TGF-beta ligand:receptor interactions","volume":"22","author":"Thompson","year":"2003","journal-title":"EMBO J."},{"issue":"2","key":"10.1016\/j.intimp.2025.115043_bb0050","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0092-8674(00)00121-5","article-title":"TGFbeta signaling in growth control, cancer, and heritable disorders","volume":"103","author":"Massagu\u00e9","year":"2000","journal-title":"Cell"},{"issue":"10","key":"10.1016\/j.intimp.2025.115043_bb0055","first-page":"2879","article-title":"Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine\/threonine kinase activity","volume":"8","author":"ten Dijke","year":"1993","journal-title":"Oncogene"},{"issue":"8","key":"10.1016\/j.intimp.2025.115043_bb0060","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S1043-2760(00)00294-0","article-title":"Activin signal transduction pathways","volume":"11","author":"Pangas","year":"2000","journal-title":"Trends Endocrinol. Metab."},{"issue":"5","key":"10.1016\/j.intimp.2025.115043_bb0065","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1210\/er.2014-1003","article-title":"Inhibin at 90: from discovery to clinical application, a historical review","volume":"35","author":"Makanji","year":"2014","journal-title":"Endocr. Rev."},{"issue":"1","key":"10.1016\/j.intimp.2025.115043_bb0070","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1152\/physrev.00002.2018","article-title":"Activin a in mammalian physiology","volume":"99","author":"Bloise","year":"2019","journal-title":"Physiol. Rev."},{"issue":"4","key":"10.1016\/j.intimp.2025.115043_bb0075","doi-asserted-by":"crossref","first-page":"G768","DOI":"10.1152\/ajpgi.90631.2008","article-title":"Upregulation of activin signaling in experimental colitis","volume":"297","author":"Zhang","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"issue":"5","key":"10.1016\/j.intimp.2025.115043_bb0080","doi-asserted-by":"crossref","DOI":"10.14309\/ctg.0000000000000152","article-title":"Activin a modulates inflammation in acute pancreatitis and strongly predicts severe disease independent of body mass index","volume":"11","author":"Thomas","year":"2020","journal-title":"Clin. Transl. Gastroenterol."},{"issue":"22","key":"10.1016\/j.intimp.2025.115043_bb0085","doi-asserted-by":"crossref","first-page":"12269","DOI":"10.1073\/pnas.1918196117","article-title":"Activin-a limits Th17 pathogenicity and autoimmune neuroinflammation via CD39 and CD73 ectonucleotidases and Hif1-\u03b1-dependent pathways","volume":"117","author":"Morianos","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"4","key":"10.1016\/j.intimp.2025.115043_bb0090","article-title":"A protocol for the induction of experimental necrotizing enterocolitis in neonatal mice","volume":"2","author":"Nolan","year":"2021","journal-title":"STAR Protoc"},{"issue":"1","key":"10.1016\/j.intimp.2025.115043_bb0095","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1053\/j.gastro.2009.03.060","article-title":"Heparin-binding EGF-like growth factor increases intestinal microvascular blood flow in necrotizing enterocolitis","volume":"137","author":"Yu","year":"2009","journal-title":"Gastroenterology"},{"issue":"1","key":"10.1016\/j.intimp.2025.115043_bb0100","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jaci.2009.05.038","article-title":"Intestinal barrier function: molecular regulation and disease pathogenesis","volume":"124","author":"Groschwitz","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"issue":"6","key":"10.1016\/j.intimp.2025.115043_bb0105","first-page":"1388","article-title":"A mouse model of pathological small intestinal epithelial cell apoptosis and shedding induced by systemic administration of lipopolysaccharide","volume":"6","author":"Williams","year":"2013","journal-title":"Dis. Model. Mech."},{"issue":"4","key":"10.1016\/j.intimp.2025.115043_bb0110","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/01.shk.0000192126.33823.87","article-title":"Cytokines in necrotizing enterocolitis","volume":"25","author":"Markel","year":"2006","journal-title":"Shock"},{"key":"10.1016\/j.intimp.2025.115043_bb0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2019.102314","article-title":"Activin-a in the regulation of immunity in health and disease","volume":"104","author":"Morianos","year":"2019","journal-title":"J. Autoimmun."},{"key":"10.1016\/j.intimp.2025.115043_bb0120","first-page":"8","article-title":"Recent advances in understanding necrotizing enterocolitis","author":"Alganabi","year":"2019","journal-title":"F1000Res"},{"issue":"8","key":"10.1016\/j.intimp.2025.115043_bb0125","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1080\/003655202760230900","article-title":"Functional relevance of activin a in the intestinal epithelium","volume":"37","author":"Dignass","year":"2002","journal-title":"Scand. J. Gastroenterol."},{"issue":"4","key":"10.1016\/j.intimp.2025.115043_bb0130","first-page":"311","article-title":"Activin a: a novel player and inflammatory marker in inflammatory bowel disease?","volume":"77","author":"H\u00fcbner","year":"1997","journal-title":"Lab. Investig."},{"issue":"1","key":"10.1016\/j.intimp.2025.115043_bb0135","doi-asserted-by":"crossref","first-page":"G89","DOI":"10.1152\/ajpgi.2000.278.1.G89","article-title":"Gene expression of activin, activin receptors, and follistatin in intestinal epithelial cells","volume":"278","author":"Sonoyama","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.intimp.2025.115043_bb0140","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jss.2024.12.003","article-title":"Estrogen alleviates oxidative bowel injury and Neuroinflammation in necrotizing enterocolitis","volume":"305","author":"Karadeniz Cerit","year":"2025","journal-title":"J. Surg. Res."},{"issue":"7","key":"10.1016\/j.intimp.2025.115043_bb0145","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1210\/en.2018-00220","article-title":"Comparing postnatal development of gonadal hormones and associated social behaviors in rats, mice, and humans","volume":"159","author":"Bell","year":"2018","journal-title":"Endocrinology"},{"issue":"2","key":"10.1016\/j.intimp.2025.115043_bb0150","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1053\/j.gastro.2004.11.063","article-title":"Therapeutic potential of follistatin for colonic inflammation in mice","volume":"128","author":"Dohi","year":"2005","journal-title":"Gastroenterology"},{"issue":"1","key":"10.1016\/j.intimp.2025.115043_bb0155","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.clp.2012.12.008","article-title":"Inflammatory signaling in necrotizing enterocolitis","volume":"40","author":"De Plaen","year":"2013","journal-title":"Clin. Perinatol."},{"issue":"4","key":"10.1016\/j.intimp.2025.115043_bb0160","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/sj.bjp.0702626","article-title":"Induction of prostanoid, nitric oxide, and cytokine formation in rat bone marrow derived macrophages by activin a","volume":"127","author":"N\u00fcsing","year":"1999","journal-title":"Br. J. Pharmacol."},{"issue":"4","key":"10.1016\/j.intimp.2025.115043_bb0165","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1203\/01.PDR.0000113463.70435.74","article-title":"Intestinal epithelial apoptosis initiates gross bowel necrosis in an experimental rat model of neonatal necrotizing enterocolitis","volume":"55","author":"Jilling","year":"2004","journal-title":"Pediatr. Res."},{"issue":"2","key":"10.1016\/j.intimp.2025.115043_bb0170","doi-asserted-by":"crossref","DOI":"10.3892\/or.2023.8688","article-title":"Activin a induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway","volume":"51","author":"Zhang","year":"2024","journal-title":"Oncol. Rep."},{"issue":"5","key":"10.1016\/j.intimp.2025.115043_bb0175","doi-asserted-by":"crossref","first-page":"3808","DOI":"10.3892\/mmr.2015.3193","article-title":"Inhibition of transforming growth factor-\u03b2 via the activin receptor-like kinase-5 inhibitor attenuates pulmonary fibrosis","volume":"11","author":"Koh","year":"2015","journal-title":"Mol. Med. Rep."},{"issue":"11","key":"10.1016\/j.intimp.2025.115043_bb0180","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1021\/acs.molpharmaceut.0c00633","article-title":"SB431542-loaded liposomes alleviate liver fibrosis by suppressing TGF-\u03b2 signaling","volume":"17","author":"Zhang","year":"2020","journal-title":"Mol. Pharm."},{"issue":"16","key":"10.1016\/j.intimp.2025.115043_bb0185","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1056\/NEJMoa2213558","article-title":"Phase 3 trial of Sotatercept for treatment of pulmonary arterial hypertension","volume":"388","author":"Hoeper","year":"2023","journal-title":"N. Engl. J. Med."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925010331?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925010331?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T20:01:58Z","timestamp":1775764918000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576925010331"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":37,"alternative-id":["S1567576925010331"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2025.115043","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Activin A exacerbates neonatal necrotizing enterocolitis via ALK4-mediated apoptosis and barrier disruption","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2025.115043","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":"115043"}}