Hepcidin and hemojuvelin gene expression in rat liver damage: in vivo and in vitro studies.
In this work, we used two rat models, partial hepatectomy (PH) and CCl(4) 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-1beta, IL-6, TNF-alpha, and IFN-gamma. 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 CCl(4) 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 CCl(4)-induced liver injury, IL-6, IL-1beta, TNF-alpha, and IFN-gamma 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-1beta but not with TNF-alpha or IFN-gamma 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.
Dept. of Internal Medicine, Univ. Hospital Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.
Nadeem
N
Sheikh
Danko S
DS
Batusic
Jozsef
J
Dudas
Kyrylo
K
Tron
Katrin
K
Neubauer
Bernhard
B
Saile
Giuliano
G
Ramadori
D000818:Animals; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D015870:Gene Expression; D000071020:Hemochromatosis Protein; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000293:injuries* / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D058851:GPI-Linked Proteins; D000071020:Hemochromatosis Protein; C513726:Hjv protein, rat; D015850:Interleukin-6; D008565:Membrane Proteins; D007501:Iron