{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:41:45Z","timestamp":1793299305112,"version":"4.5.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2679,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO)"},{"name":"Mochida Memorial Foundation"},{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Yamanouchi Foundation of Research on Metabolic Disorders"},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kato Memorial Foundation"},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Japan Intractable Disease Research Foundation"},{"name":"Ichiro Kanehara Memorial Foundation"},{"name":"NOVARTIS Foundation (Japan) for Promotion of Science"},{"name":"Mitsubishi Pharma Research Foundation"},{"name":"Clinical Research Foundation (2007)"},{"name":"Yakulto Bioscience Research Foundation"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Acute liver failure is associated with significant mortality. However, the underlying pathophysiological mechanism is not yet fully understood. Suppressor of cytokine signaling-1 (SOCS1), which is a negative-feedback molecule for cytokine signaling, has been shown to be rapidly induced during liver injury. Here, using liver-specific SOCS1-conditional-knockout mice, we demonstrated that SOCS1 deletion in hepatocytes enhanced concanavalin A (ConA)\u2013induced hepatitis, which has been shown to be dependent on activated T and natural killer T (NKT) cells. Although serum cytokine level and NKT cell activation were similar in wild-type (WT) and SOCS1-deficient mice after ConA treatment, proapoptotic signals, including signal transducers and activators of transcription 1 (STAT1) and Jun-terminal kinase (JNK) activation, were enhanced in SOCS1-deficient livers compared with those in WT livers. SOCS1-deficient hepatocytes had higher expression of Fas antigen and were more sensitive to anti-Fas antibody\u2013induced apoptosis than were WT hepatocytes. Furthermore, SOCS1-deficient hepatocytes were more sensitive to tumor necrosis factor (TNF)-\u03b1-induced JNK activation and apoptosis. These data indicate that SOCS1 is important to the prevention of hepatocyte apoptosis induced by Fas and TNF-\u03b1. In contrast, SOCS1 overexpression in the liver by adenoviral gene transfer prevented ConA-induced liver injury.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>These findings indicate that SOCS1 plays important negative roles in fulminant hepatitis and that forced expression of SOCS1 is therapeutic in preventing hepatitis.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.22214","type":"journal-article","created":{"date-parts":[[2008,2,7]],"date-time":"2008-02-07T15:18:33Z","timestamp":1202397513000},"page":"1644-1654","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":43,"title":["Suppressor of cytokine signaling 1 protects mice against concanavalin A\u2013induced hepatitis by inhibiting apoptosis"],"prefix":"10.1097","volume":"47","author":[{"given":"Takehiro","family":"Torisu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Nakaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatoshi","family":"Chinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyuki","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikatsu","family":"Hanada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Torisu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giichi","family":"Takaesu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yasukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-24-20241201","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11894-003-0008-8","article-title":"Etiology and management of fulminant hepatic failure.","volume":"5","author":"Vaquero","year":"2003","journal-title":"Curr Gastroenterol Rep"},{"key":"R2-24-20241201","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1111\/j.1572-0241.2000.02268.x","article-title":"Significance of Fas antigenmediated apoptosis in human fulminant hepatic failure.","volume":"95","author":"Ryo","year":"2000","journal-title":"Am J Gastroenterol"},{"key":"R3-24-20241201","doi-asserted-by":"crossref","first-page":"5498","DOI":"10.1073\/pnas.040566697","article-title":"Critical contribution of liver natural killer T cells to a murine model of hepatitis.","volume":"97","author":"Takeda","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R4-24-20241201","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1172\/JCI0215841","article-title":"Opposing roles of STAT1 and STAT3 in T cellmediated hepatitis: regulation by SOCS.","volume":"110","author":"Hong","year":"2002","journal-title":"J Clin Invest"},{"key":"R5-24-20241201","doi-asserted-by":"crossref","first-page":"G583","DOI":"10.1152\/ajpgi.00422.2005","article-title":"Mechanisms of Liver Injury. I. TNFalphainduced liver injury: role of IKK, JNK, and ROS pathways.","volume":"290","author":"Schwabe","year":"2006","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R6-24-20241201","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/nri2093","article-title":"SOCS proteins, cytokine signalling and immune regulation.","volume":"7","author":"Yoshimura","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"R7-24-20241201","doi-asserted-by":"crossref","first-page":"15577","DOI":"10.1073\/pnas.95.26.15577","article-title":"Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI1 (STATinduced STAT inhibitor1) deficient mice.","volume":"95","author":"Naka","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R8-24-20241201","doi-asserted-by":"crossref","first-page":"14395","DOI":"10.1073\/pnas.95.24.14395","article-title":"Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling1.","volume":"95","author":"Starr","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R9-24-20241201","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S1074-7613(01)00132-7","article-title":"SOCS1SSI1deficient NKT cells participate in severe hepatitis through dysregulated crosstalk inhibition of IFNgamma and IL4 signaling in vivo.","volume":"14","author":"Naka","year":"2001","journal-title":"Immunity"},{"key":"R10-24-20241201","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1084\/jem.20031675","article-title":"SOCS1 is a suppressor of liver fibrosis and hepatitisinduced carcinogenesis.","volume":"199","author":"Yoshida","year":"2004","journal-title":"J Exp Med"},{"key":"R11-24-20241201","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1365-2443.2007.01044.x","article-title":"The dual function of hepatic SOCS3 in insulin resistance in vivo.","volume":"12","author":"Torisu","year":"2007","journal-title":"Genes 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protein.","volume":"23","author":"Kamio","year":"2004","journal-title":"Oncogene"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.22214","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200805000-00024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T14:15:03Z","timestamp":1733062503000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200805000-00024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.22214","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2008,5]]}}}