Submitted on May 30, 2003
Accepted on October 24, 2003
HEPCIDIN REGULATION OF FERROPORTIN 1 EXPRESSION IN THE LIVER AND INTESTINE OF THE RAT
Kwo-yih Yeh1*, Mary Yeh2, and Jonathan Glass2
1 Departments of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA; Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA; The Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA
2 Departments of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA; The Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, USA
* To whom correspondence should be addressed. E-mail: kyeh{at}lsuhsc.edu.
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 lipopolysaccharide (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 h and 36 h. Concurrent ly 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. While the initial decrease of FPT1 coincides with a LPS-induced decrease in
serum iron, both intestinal and hepatic FPT1 expression recovered while serum iron
concentration continued to decrease for at least 24 hours. 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 His-rHepc
induced significant reduction of intestinal FPT1 expression. Taken together, the data
suggest that hepcidin mediates LPS-induced down regulation of intestinal FPT1 expression and
that the hepcidin signaling pathway involves a PDTC-sensitive step.
