Submitted on December 25, 2005
Accepted on March 17, 2006
Hepcidin and Hemojuvelin gene-expression in rat liver damage:
In vivo and in vitro studies
Nadeem Sheikh1, Danko S Batusic1, Jozsef Dudas1, Kyrylo Tron1, Katrin Neubauer1, Bernhard Saile1, and Giuliano Ramadori1*
1 Department of Medicine, Division of Gastroenterology and Endocrinology,, University hospital, Gottingen, Germany
* To whom correspondence should be addressed. E-mail: gramado{at}med.uni-goettingen.de.
In this work we have used two rat models, partial hepatectomy (PH) and CCl4-administration to study the changes in iron pathway in response to hepatic damage. Liver injury induced changes in the hepatic gene expression of hepcidin, Hjv, several other proteins of iron metabolism, and also of several cytokines such as IL-1
, IL-6, TNF-
and IFN-
. Hepcidin-gene-expression was upregulated between 4 and 8 hours with a maximum up to 16 hours after surgery. However, Hjv-gene-expression was downregulated at the same time. An early upregulation of hepcidin- (3 hours) and downregulation of Hjv-gene-expression was found after CCl4-administration. TfR1- and ferritin-H-gene-expression was upregulated whereas the Fpn.-1-gene-expression was downregulated. Hepatic IL-6-gene-expression was upregulated early after PH and reached maximum 8 hours after the PH. In CCl4-induced liver injury IL-6, IL-1, TNF- and IFN- upregulation was found at the maximum 12 hours after 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 the hepcidin- and downregulated the Hjv-gene-expression.
Conclusion: In hepatic damage changes of the hepatic-gene-expression of the main proteins involved in iron-metabolism may be induced by locally synthesized mediators.
