{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:49:19Z","timestamp":1788299359010,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The role of activin B, a transforming growth factor \u03b2 (TGF\u03b2) superfamily cytokine, in liver health and disease is largely unknown. We aimed to investigate whether activin B modulates liver fibrogenesis. Liver and serum activin B, along with its analog activin A, were analyzed in patients with liver fibrosis from different etiologies and in mouse acute and chronic liver injury models. Activin B, activin A, or both was immunologically neutralized in mice with progressive or established carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )\u2013induced liver fibrosis. Hepatic and circulating activin B was increased in human patients with liver fibrosis caused by several liver diseases. In mice, hepatic and circulating activin B exhibited persistent elevation following the onset of several types of liver injury, whereas activin A displayed transient increases. The results revealed a close correlation of activin B with liver injury regardless of etiology and species. Injured hepatocytes produced excessive activin B. Neutralizing activin B largely prevented, as well as improved, CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced liver fibrosis, which was augmented by co\u2010neutralizing activin A. Mechanistically, activin B mediated the activation of c\u2010Jun\u2010N\u2010terminal kinase (JNK), the induction of inducible nitric oxide synthase (iNOS) expression, and the maintenance of poly (ADP\u2010ribose) polymerase 1 (PARP1) expression in injured livers. Moreover, activin B directly induced a profibrotic expression profile in hepatic stellate cells (HSCs) and stimulated these cells to form a septa structure.\n                    <jats:italic toggle=\"yes\">Conclusions<\/jats:italic>\n                    : We demonstrate that activin B, cooperating with activin A, mediates the activation or expression of JNK, iNOS, and PARP1 and the activation of HSCs, driving the initiation and progression of liver fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/hep4.2037","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T07:04:29Z","timestamp":1658473469000},"page":"2812-2826","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Activin B promotes the initiation and progression of liver fibrosis"],"prefix":"10.1097","volume":"6","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biology,School of Science,Center for Developmental and Regenerative Biology,Indiana University\u2013Purdue University Indianapolis,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Hamang","sequence":"additional","affiliation":[{"name":"Department of Biology,School of Science,Center for Developmental and Regenerative Biology,Indiana University\u2013Purdue University Indianapolis,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5740-6579","authenticated-orcid":false,"given":"Alexander","family":"Culver","sequence":"additional","affiliation":[{"name":"Department of Biology,School of Science,Center for Developmental and Regenerative Biology,Indiana University\u2013Purdue University Indianapolis,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaizhou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biology,School of Science,Center for Developmental and Regenerative Biology,Indiana University\u2013Purdue University Indianapolis,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Yanum","sequence":"additional","affiliation":[{"name":"Department of Biology,School of Science,Center for Developmental and Regenerative Biology,Indiana University\u2013Purdue University Indianapolis,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Biology,School of Science,Center for Developmental and Regenerative Biology,Indiana University\u2013Purdue University 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Medicine,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-3178","authenticated-orcid":false,"given":"Naga","family":"Chalasani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6504-8123","authenticated-orcid":false,"given":"Suthat","family":"Liangpunsakul","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine,Indianapolis,Indiana,USA"},{"name":"Department of Biochemistry and Molecular Biology,Indiana University School of Medicine,Indianapolis,Indiana,USA"},{"name":"Roudebush Veterans Administration Medical 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