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Hepcidin and hemojuvelin gene expression in rat liver damage: in vivo and in vitro studies

Division of Gastroenterology and Endocrinology, Department of Medicine, University Hospital, Georg-August-University, Göttingen, Germany

Submitted 27 December 2005 ; accepted in final form 17 March 2006

In this work, we used two rat models, partial hepatectomy (PH) and CCl₄ administration, to study the changes in iron pathways in response to hepatic damage. Liver injury induced changes in the hepatic gene expression of hepcidin, hemojuvelin (Hjv), several other proteins of iron metabolism, and several cytokines such as IL-1, IL-6, TNF-, and IFN-. Hepcidin gene expression was upregulated between 4 and 8 h with a maximum up to 16 h after surgery. However, Hjv gene expression was downregulated at the same time. An early upregulation of hepcidin (3 h) and downregulation of Hjv gene expression was found after CCl₄ administration. Transferrin receptor 1 and ferritin H gene expression was upregulated, whereas ferroportin 1 gene expression was downregulated. Hepatic IL-6 gene expression was upregulated early after PH and reached maximum 8 h after the PH. In CCl₄-induced liver injury, IL-6, IL-1, TNF-, and IFN- upregulation were found at the maximum 12 h after the administration of the toxin. Treatment of isolated rat hepatocytes with IL-6 and, to a lesser extent, with IL-1 but not with TNF- or IFN- dose dependently upregulated hepcidin and downregulated Hjv gene expression. In hepatic damage, changes of the hepatic gene expression of the main proteins involved in iron metabolism may be induced by locally synthesized mediators.

partial hepatectomy; CCl₄; iron metabolism

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				H. Christiansen, N. Sheikh, B. Saile, F. Reuter, M. Rave-Frank, R. M. Hermann, J. Dudas, A. Hille, C. F. Hess, and G. Ramadori x-Irradiation in Rat Liver: Consequent Upregulation of Hepcidin and Downregulation of Hemojuvelin and Ferroportin-1 Gene Expression Radiology, December 1, 2006; 242(1): 189 - 197. [Abstract] [Full Text] [PDF]