{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:00:15Z","timestamp":1765609215576},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,3,24]],"date-time":"2003-03-24T00:00:00Z","timestamp":1048464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2003,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Leptin is a 16\u2010kDa hormone with an array of biologic actions. We, and others, have demonstrated that leptin is critical to the development of liver fibrogenesis both in vitro and in the lean littermates of <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice exposed to carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>). Controversy exists as to whether leptin can act as a direct cytokine in the development of increased collagen expression, and whether <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mice are resistant to potential injury from CCl<jats:sub>4<\/jats:sub>. Here, we provide evidence that strongly suggests that leptin acts to increase nascent production of mRNA for the \u03b12(I) collagen gene based upon ribonuclease protection analysis (RPA). Actinomycin D, but not cyclohexamide, or the pan\u2010neutralizing antibody to transforming growth factor beta one (TGF\u03b21), significantly diminished the effect of leptin on total \u03b12(I) collagen mRNA levels. Further evidence that leptin acts directly on HSCs to alter gene expression in liver wounding is demonstrated by enhanced binding of phosphorylated signal transduction and activator of transcription factor 3 (pStat3) to a cis\u2010inducible element (SIE) oligonucleotide by electrophoretic mobility shift assay (EMSA). This consensus sequence is responsible for production of a critical collagen transcription factor, AP\u20101. Finally, we have demonstrated from the <jats:italic>ob<\/jats:italic>\/<jats:italic>ob<\/jats:italic> mouse model that these animals are at least as sensitive to CCl<jats:sub>4<\/jats:sub> as their respective lean animals as assessed by serum alanine aminotransferase (ALT) measurements. Taken together, the current data provide a continued framework that leptin is a profibrogenic cytokine and plays a key role in liver fibrosis. J. Cell. Biochem. 89: 311\u2013320, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.10494","type":"journal-article","created":{"date-parts":[[2003,4,16]],"date-time":"2003-04-16T10:45:31Z","timestamp":1050489931000},"page":"311-320","source":"Crossref","is-referenced-by-count":71,"title":["Leptin induces increased \u03b12(I) collagen gene expression in cultured rat hepatic stellate cells"],"prefix":"10.1002","volume":"89","author":[{"given":"Neeraj K.","family":"Saxena","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Saliba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey J.","family":"Floyd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank A.","family":"Anania","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,4,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840210624"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3040817"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118055"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7624778"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.11.1455"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-12927"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3272"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007111"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977190109001078"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(89)80067-0"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.4.2247"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90673-7"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(02)00723-0"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840170411"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.2741\/gressner"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.33684"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32995"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01002772"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1999.276.4.G1059"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2125"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.21.4306"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)80175-4"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7624776"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.17894"},{"key":"e_1_2_5_28_1","doi-asserted-by":"crossref","first-page":"15457","DOI":"10.1016\/S0021-9258(18)98638-2","article-title":"The upstream stimulatory factor binds to and activate the promoter of the rat class I alcohol dehydrogenase gene","volume":"266","author":"Potter JJ","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(91)90356-N"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(96)80238-8"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.27126"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90282-1"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.32029"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1683"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.9.5201"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02300-8"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.1760"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2002.29865"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/372425a0"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.10494","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.10494","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T18:54:56Z","timestamp":1700247296000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.10494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4,15]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,5,15]]}},"alternative-id":["10.1002\/jcb.10494"],"URL":"https:\/\/doi.org\/10.1002\/jcb.10494","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4,15]]}}}