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To study the largely unknown regulation of iron metabolism in the context of hepatic disease, we used two established models of chronic liver injury, ie repeated carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CCl<jats:sub>4<\/jats:sub><\/jats:styled-content>) or thioacetamide (<jats:styled-content style=\"fixed-case\">TAA<\/jats:styled-content>) injections. To determine the impact of <jats:styled-content style=\"fixed-case\">CCAAT<\/jats:styled-content>\/enhancer\u2010binding protein (C\/<jats:styled-content style=\"fixed-case\">EBP<\/jats:styled-content>)\u2010homologous protein (<jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>) on hepcidin production, the effect of a single <jats:styled-content style=\"fixed-case\">TAA<\/jats:styled-content> injection was determined in wild\u2010type and <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> knockout mice. Furthermore, <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> and hepcidin expression was assessed in control subjects and patients with alcoholic liver disease. Both chronic injury models developed a distinct iron overload in macrophages. <jats:styled-content style=\"fixed-case\">TAA<\/jats:styled-content>\u2010, but not <jats:styled-content style=\"fixed-case\">CCl<jats:sub>4<\/jats:sub><\/jats:styled-content>\u2010 injected mice displayed additional iron accumulation in hepatocytes, resulting in a significant hepatic and systemic iron overload which was due to suppressed hepcidin levels. C\/<jats:styled-content style=\"fixed-case\">EBP\u03b1<\/jats:styled-content> signalling, a known hepcidin inducer, was markedly inhibited in <jats:styled-content style=\"fixed-case\">TAA<\/jats:styled-content> mice, due to lower C\/<jats:styled-content style=\"fixed-case\">EBP\u03b1<\/jats:styled-content> levels and overexpression of <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>, a C\/<jats:styled-content style=\"fixed-case\">EBP\u03b1<\/jats:styled-content> inhibitor. A single <jats:styled-content style=\"fixed-case\">TAA<\/jats:styled-content> injection resulted in a long\u2010lasting (&gt; 6 days) suppression of hepcidin levels and <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> knockouts (compared to wild\u2010types) displayed significantly attenuated hepcidin down\u2010regulation in response to acute <jats:styled-content style=\"fixed-case\">TAA<\/jats:styled-content> administration. <jats:italic>CHOP<\/jats:italic> mRNA levels increased 5\u2010fold in alcoholic liver disease patients versus controls (<jats:italic>p<\/jats:italic> &lt; 0.005) and negatively correlated with hepcidin expression. Our results establish <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> as an important regulator of hepatic hepcidin expression in chronic liver disease. The differences in iron metabolism between the two widely used fibrosis models likely reflect the differential regulation of hepcidin expression in human liver disease. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4221","type":"journal-article","created":{"date-parts":[[2013,6,8]],"date-time":"2013-06-08T09:58:40Z","timestamp":1370685520000},"page":"532-542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp>CHOP<\/scp>\u2010mediated hepcidin suppression modulates hepatic iron load"],"prefix":"10.1002","volume":"231","author":[{"given":"Katrin","family":"Mueller","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I University Hospital Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Sunami","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry University of Ulm Germany"},{"name":"Department of General Surgery, Klinikum Rechts der Isar Technical University Munich 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