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Blood, 15 January 2008, Vol. 111, No. 2, pp. 924-931. Prepublished online as a Blood First Edition Paper on October 15, 2007; DOI 10.1182/blood-2007-07-100677. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-07-100677v1 111/2/924    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Silvestri, L. Articles by Camaschella, C. Search for Related Content PubMed PubMed Citation Articles by Silvestri, L. Articles by Camaschella, C. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis Laura Silvestri1, Alessia Pagani1, and Clara Camaschella1 1 Vita-Salute San Raffaele University–Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele, Milan, Italy The liver peptide hepcidin regulates iron absorption and recycling. Hemojuvelin (HJV) has a key role in hepcidin regulation, and its inactivation causes severe iron overload both in humans and in mice. Membrane HJV (m-HJV) acts as a coreceptor for bone morphogenetic proteins (BMPs), whereas soluble HJV (s-HJV) may down-regulate hepcidin in a competitive way interfering with BMP signaling. s-HJV is decreased by iron in vitro and increased by iron deficiency in vivo. However, the mechanisms regulating the 2 HJV isoforms remain unclear. Here we show that s-HJV originates from a furin cleavage at position 332–335. s-HJV is reduced in the cleavage mutant R335Q as well as in cells treated with a furin inhibitor, and increased in cells overexpressing exogenous furin, but not in cells overexpressing an inactive furin variant. Furin is up-regulated by iron deficiency and hypoxia in association with the stabilization of HIF-1. Increased s-HJV in response to HIF-1 occurs during differentiation of murine muscle cells expressing endogenous Hjv. Our data are relevant to the mechanisms that relate iron metabolism to the hypoxic response. The release of s-HJV might be a tissue-specific mechanism, signaling the local iron requests of hypoxic skeletal muscles independently of the oxygen status of the liver. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. W. Swinkels and J. F. M. Wetzels Hepcidin: a new tool in the management of anaemia in patients with chronic kidney disease? Nephrol. Dial. Transplant., May 21, 2008; (2008) gfn267v1. [Full Text] [PDF] R. Kuns-Hashimoto, D. Kuninger, M. Nili, and P. Rotwein Selective binding of RGMc/hemojuvelin, a key protein in systemic iron metabolism, to BMP-2 and neogenin Am J Physiol Cell Physiol, April 1, 2008; 294(4): C994 - C1003. [Abstract] [Full Text] [PDF]

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