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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2182-2189. Prepublished online as a Blood First Edition Paper on May 31, 2007; DOI 10.1182/blood-2007-04-087593. This Article Full Text (PDF) All Versions of this Article: blood-2007-04-087593v1 110/6/2182    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lin, L. Articles by Ganz, T. Search for Related Content PubMed PubMed Citation Articles by Lin, L. Articles by Ganz, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 30, 2007 Accepted May 30, 2007 Iron-transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4 Lan Lin, Erika V Valore, Elizabeta Nemeth, Julia B Goodnough, Victoria Gabayan, and Tomas Ganz* Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States * Corresponding author; email: tganz{at}mednet.ucla.edu. The peptide hormone hepcidin is the principal regulator of systemic iron homeostasis. We examined the pathway by which iron stimulates the production of hepcidin. In humans who ingested 65 mg of iron, the increase in transferrin saturation preceded by hours the increase in urinary hepcidin excretion. Increases in urinary hepcidin concentrations were proportional to the increment in transferrin saturation. Paradoxically, in previous studies in primary hepatocytes and cell lines, hepcidin response to iron or iron-transferrin was not observed. We now report that freshly isolated murine primary hepatocytes responded to holotransferrin but not apotransferrin by increasing hepcidin mRNA. Hepcidin increase was not due to contamination of the transferrin preparations by endotoxin, a potent pathological stimulus of hepcidin synthesis. Using this culture system, we showed that holotransferrin concentrations regulate hepcidin mRNA concentrations through a hemojuvelin / BMP2/4-dependent pathway. Although BMP9 is known to be expressed in the liver and potently increased the basal concentrations of hepcidin mRNA, it did not interact with hemojuvelin, and interference with its signaling pathway did not affect iron regulation. Fresh primary hepatocytes constitute a sufficient system for the regulation of hepcidin by physiologic iron stimuli, and will greatly facilitate studies of major disorders of iron homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Iron can boost hepcidin both ways Prem Ponka and Bill Andriopoulos Blood 2007 110: 1703-1704. [Full Text] [PDF] This article has been cited by other articles: M. B Zimmermann, B. Troesch, R. Biebinger, I. Egli, C. Zeder, and R. F Hurrell Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin Am. J. Clinical Nutrition, November 1, 2009; 90(5): 1280 - 1287. [Abstract] [Full Text] [PDF] B. Young and J. Zaritsky Hepcidin for Clinicians Clin. J. Am. Soc. Nephrol., August 1, 2009; 4(8): 1384 - 1387. [Abstract] [Full Text] [PDF] T. Tanno, P. Porayette, O. 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