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This Article Full Text Full Text (PDF) All Versions of this Article: JOE-09-0191v1 202/3/389    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Schwarz, P. Articles by Kulaksiz, H. PubMed PubMed Citation Articles by Schwarz, P. Articles by Kulaksiz, H.

Division of Gastroenterology, Department of Internal Medicine, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm, Germany
¹ Division of Gastroenterology, Department of Internal Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany

(Correspondence should be addressed to H Kulaksiz; Email: hasan.kulaksiz{at}uniklinik-ulm.de)

Hepcidin, a cysteine-rich peptide hormone with antimicrobial and iron-regulatory activity, plays a central role in regulating iron metabolism during inflammation, hypoxia, iron deficiency, and iron overload. The aim of this study was to isolate and sequence the guinea pig hepcidin gene and show peptide's tissue distribution to identify the guinea pig as good animal model to study the regulation and function of hepcidin. The guinea pig hepcidin cDNA contains a 252 bp open reading frame encoding for an 83 amino acid protein with eight highly conserved cysteine residues. Phylogenetic analyses showed that guinea pig hepcidin was more related to human and chimpanzee than to rodents like mouse or rat. RT-PCR studies revealed that hepcidin mRNA was most abundant in liver, less ample in pancreas, heart, and kidney and not detectable in lung and biliary system. Western blot analyses showed a distinct immunoreactive band of 8 kDa, consistent with the predicted size of prohepcidin, and revealed that guinea pig hepcidin protein is synthesized predominantly in the liver, and with lower expression in kidney, heart, and pancreas. Immunohistochemical studies showed hepcidin predominantly at the basolateral membrane domain of hepatocytes in periportal regions. In pancreas, hepcidin immunoreactivity was confined to endocrine islets of Langerhans, while hepcidin was seen in tubules, but not in the glomeruli in the kidney. Our data identify guinea pig as a convenient model organism to study the role of hepcidin, given the remarkable sequence similarity and tissue distribution pattern largely identical to human.