RGD Reference Report - Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat. - Rat Genome Database

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Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat.

Authors: Yeh, KY  Yeh, M  Glass, J 
Citation: Yeh KY, etal., Am J Physiol Gastrointest Liver Physiol 2004 Mar;286(3):G385-94. Epub 2003 Oct 30.
RGD ID: 1304454
Pubmed: PMID:14592944   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpgi.00246.2003   (Journal Full-text)

Hepcidin has been implicated as the iron stores regulator: a hepatic signaling molecule that regulates intestinal iron absorption by undefined mechanisms. The possibility that hepcidin regulates the expression of ferroportin 1 (FPT1), the basolateral iron transporter, was examined in rats after administration of LPS, an iron chelator, or His-tagged recombinant hepcidin (His-rHepc). In the liver, LPS stimulated a biphasic increase of hepcidin mRNA with peaks of mRNA at 6 and 36 h. Concurrently, hepatic FPT1 mRNA expression decreased to minimal level at 6 h and then increased with a peak at 24-36 h. LPS also induced biphasic changes in intestinal FPT1 mRNA expression, with decreased levels at 6 h and increased expression at 48 h. Whereas the initial decrease of FPT1 coincides with an LPS-induced decrease in serum iron, both intestinal and hepatic FPT1 expression recovered, whereas serum iron concentration continued to decrease for at least 24 h. Dietary iron ingestion increased intestinal ferritin protein production but did not reduce intestinal FPT1 mRNA expression. The iron chelator pyrrolidinedithiocarbamate (PDTC) stimulated hepatic hepcidin without suppressing intestinal FPT1 expression. In PDTC-treated rats, LPS stimulated no additional hepatic hepcidin expression but did increase intestinal FPT1 expression. Administration of HisrHepc induced significant reduction of intestinal FPT1 expression. Taken together, these data suggest that hepcidin mediates LPS-induced downregulation of intestinal FPT1 expression and that the hepcidin signaling pathway involves a PDTC-sensitive step.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
intracellular iron ion homeostasis  IDA 1304454 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hamp  (hepcidin antimicrobial peptide)

Objects referenced in this article
Gene Slc40a1 solute carrier family 40 member 1 Rattus norvegicus

Additional Information