{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T09:46:37Z","timestamp":1776505597612,"version":"3.51.2"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,1,31]],"date-time":"2012-01-31T00:00:00Z","timestamp":1327968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previous studies demonstrated that the <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>ong\u2010<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>vans (<jats:styled-content style=\"fixed-case\">LE<\/jats:styled-content>) rats exhibited liver injury and lipid metabolic abnormalities after 8\u00a0weeks of ethanol feeding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The goal of this study was to investigate if the <jats:styled-content style=\"fixed-case\">LE<\/jats:styled-content> rats develop more advanced hepatic abnormalities (e.g., fibrosis) after long\u2010term feeding with an ethanol\u2010containing <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>ieber\u2013<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>e<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>arli diet. In addition, the contribution of early growth response\u20101 (<jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1) transcription factor to these pathological changes was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>ong\u2010<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>vans rats were fed an ethanol\u2010containing or isocaloric control liquid diet for 18\u00a0months. Livers were processed for histological analyses, studies of fibrosis\u2010related gene expression, cell fractionation and triglyceride measurement. Serum alanine aminotransferase (<jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content>) levels were assessed. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> binding activities of p53 and the sterol regulatory element\u2010binding protein\u20101c (<jats:styled-content style=\"fixed-case\">SREBP<\/jats:styled-content>1c) were analysed. The abundance of <jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1 and enzymes involved in fatty acid synthesis were determined. Chromatin immunoprecipitation was employed to study <jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1 binding to the <jats:styled-content style=\"fixed-case\">SREBP<\/jats:styled-content>1c promoter region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ethanol feeding generated steatosis, chicken wire fibrosis and <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> elevations in the <jats:styled-content style=\"fixed-case\">LE<\/jats:styled-content> rats. Fibrosis was associated with the upregulation of <jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1 and its downstream target genes. <jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1 upregulation was associated with enhanced p53 activity and an increase in the cellular p66<jats:sup>shc<\/jats:sup> abundance. Steatosis was linked to the activation of <jats:styled-content style=\"fixed-case\">SREBP<\/jats:styled-content>1c. Importantly, <jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1 upregulation paralleled the expression and transcriptional activity of <jats:styled-content style=\"fixed-case\">SREBP<\/jats:styled-content>1c. Finally, <jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1 was shown to bind to the <jats:styled-content style=\"fixed-case\">SREBP<\/jats:styled-content>1c promoter region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Long\u2010term ethanol feeding promoted steatosis and fibrosis in <jats:styled-content style=\"fixed-case\">LE<\/jats:styled-content> rats via <jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1 activation. The highly abundant <jats:styled-content style=\"fixed-case\">EGR<\/jats:styled-content>1 bound to the <jats:styled-content style=\"fixed-case\">SREBP<\/jats:styled-content>1c promoter and contributed to the steatosis observed in the <jats:styled-content style=\"fixed-case\">LE<\/jats:styled-content> rat model.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1478-3231.2012.02752.x","type":"journal-article","created":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T02:18:20Z","timestamp":1328062700000},"page":"761-770","source":"Crossref","is-referenced-by-count":20,"title":["Early growth response\u20101 transcription factor promotes hepatic fibrosis and steatosis in long\u2010term ethanol\u2010fed <scp>L<\/scp>ong\u2010<scp>E<\/scp>vans rats"],"prefix":"10.1111","volume":"32","author":[{"given":"Zoltan","family":"Derdak","sequence":"first","affiliation":[{"name":"Division of Gastroenterology &amp; Liver Research Center Warren Alpert Medical School of Brown University and Rhode Island Hospital Providence RI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine A.","family":"Villegas","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology &amp; Liver Research Center Warren Alpert Medical School of Brown University and Rhode Island Hospital Providence RI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack R.","family":"Wands","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology &amp; Liver Research Center Warren Alpert Medical School of Brown University and Rhode Island Hospital Providence RI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.41.6.845"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1521-6918(03)00033-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI105200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840050212"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.08.007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0053"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.11.042"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.6148"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2011.03.005"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7700896"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2006.12.004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311668200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50368"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.011"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069004"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.44"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202411200"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2004.07.004"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.09.049"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01607.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00575.2007"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.03.005"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.02.065"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000459999"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.122978"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00865.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0503com"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00456.2009"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1478-3231.2012.02752.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1478-3231.2012.02752.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T04:22:02Z","timestamp":1698639722000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1478-3231.2012.02752.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,31]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1111\/j.1478-3231.2012.02752.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1478-3231.2012.02752.x","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,31]]}}}