Transferrin receptor 2 and HFE regulate furin expression via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) signaling. Implications for transferrin-dependent hepcidin regulation.

Haematologica
Maura PoliPaolo Arosio

Abstract

Impaired regulation of hepcidin in response to iron is the cause of genetic hemochromatosis associated with defects of HFE and transferrin receptor 2. However, the role of these proteins in the regulation of hepcidin expression is unclear. Hepcidin expression, SMAD and extracellular signal-regulated kinase (Erk) phosphorylation and furin expression were analyzed in hepatic HepG2 cells in which HFE and transferrin receptor 2 were down-regulated or expressed, or furin activity specifically inhibited. Furin expression was also analyzed in the liver of transferrin receptor 2 null mice. We showed that the silencing of HFE and transferrin receptor 2 reduced both Erk phosphorylation and furin expression, that the exogenous expression of the two enhanced the induction of phosphoErk1/2 and furin by holotransferrin, but that this did not occur when the pathogenic HFE mutant C282Y was expressed. Furin, phosphoErk1/2 and phosphoSMAD1/5/8 were down-regulated also in transferrin receptor 2-null mice. Treatment of HepG2 cells with an inhibitor of furin activity caused a strong suppression of hepcidin mRNA, probably due to the inhibition of bone morphogenic protein maturation. The data indicate that transferrin receptor 2 and HFE are involved ...Continue Reading

References

Mar 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·J N FederR C Schatzman
Jul 11, 1998·The Journal of Biological Chemistry·M F FavataJ M Trzaskos
Jan 13, 1999·The Journal of Cell Biology·D B Constam, E J Robertson
Dec 23, 2003·Cellular Signalling·Anja NoheNils O Petersen
Oct 9, 2004·The Journal of Biological Chemistry·Anton J M RoebroekJohn W M Creemers
Mar 2, 2005·Best Practice & Research. Clinical Haematology·Tomas Ganz
Aug 17, 2005·The Journal of Biological Chemistry·An-Sheng ZhangCaroline A Enns
Apr 11, 2006·Nature Genetics·Jodie L BabittHerbert Y Lin
Jun 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jaroslav TruksaErnest Beutler
Oct 3, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nathalie ScamuffaAbdel-Majid Khatib
Jul 4, 2007·The Journal of Clinical Investigation·Ivana De DomenicoJerry Kaplan
Jul 4, 2007·The Journal of Clinical Investigation·Jodie L BabittHerbert Y Lin
Oct 2, 2007·Blood Cells, Molecules & Diseases·Erika V Valore, Tomas Ganz
Nov 21, 2007·Nature Chemical Biology·Paul B YuRandall T Peterson
Mar 5, 2008·Cell Metabolism·Paul J SchmidtNancy C Andrews
Apr 9, 2008·Current Opinion in Hematology·Elizabeta Nemeth
Jul 9, 2008·Blood·Nancy C Andrews
Mar 3, 2009·Nature Genetics·Billy AndriopoulosJodie L Babitt
Mar 3, 2009·Nature Genetics·Delphine MeynardMarie-Paule Roth
Oct 14, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Daniel F WallaceV Nathan Subramaniam

❮ Previous
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Citations

Aug 1, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alina DabaKostas Pantopoulos
Jun 19, 2012·Biochemistry·Kostas PantopoulosL Devireddy
Jan 27, 2012·The New England Journal of Medicine·Robert E Fleming, Prem Ponka
Jan 1, 2014·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Takeshi IzawaJyoji Yamate
Oct 26, 2013·The American Journal of the Medical Sciences·Cindy N Roy
Jan 17, 2012·Blood Cells, Molecules & Diseases·Pauline LeeHongfan Peng
Apr 14, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Elena CorradiniJodie L Babitt
May 28, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anita C G ChuaJohn K Olynyk
Jun 8, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Víctor DíazGaetano Cairo
Jun 26, 2015·Cell Biology International·Attila MisetaKatalin Sipos
Jun 26, 2013·Experimental Neurology·María Julia PérezJuana María Pasquini
Jan 31, 2015·Experimental Hematology·Hiroshi KawabataAkifumi Takaori-Kondo
Aug 26, 2011·Biochimica Et Biophysica Acta·Juxing Chen, Caroline A Enns
Jan 22, 2015·Antioxidants & Redox Signaling·Qian WuFudi Wang
Mar 15, 2014·Virulence·Urania GeorgopoulouAvgi Mamalaki
Jan 23, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Patricia KentKostas Pantopoulos
Nov 10, 2013·Blood·Delphine MeynardHerbert Y Lin
Nov 12, 2014·Metallomics : Integrated Biometal Science·Robert J Simpson, Andrew T McKie
May 9, 2014·Frontiers in Pharmacology·Maura PoliPaolo Arosio
May 23, 2014·Frontiers in Pharmacology·Laura SilvestriClara Camaschella
Apr 12, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maura PoliPaolo Arosio
Jan 18, 2018·American Journal of Physiology. Cell Physiology·Kristoffer B SuggChristopher L Mendias
Apr 18, 2014·American Journal of Physiology. Renal Physiology·Aritoshi KidaTakeshi Nakanishi
Sep 29, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Moussa KenawiOlivier Loréal
Oct 27, 2018·Pharmaceuticals·Antonella RoettoRosa Maria Pellegrino
Apr 9, 2019·Blood Research·Negin Shokrgozar, Habib Allah Golafshan
Nov 29, 2011·Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine·Yutaka Kohgo
Mar 7, 2021·Cells·Marceau QuatredeniersFrédéric Perros
Dec 24, 2020·International Journal of Molecular Sciences·Cyrielle Richard, Frédérique Verdier
May 17, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Allison L Fisher, Jodie L Babitt
Aug 15, 2021·Seminars in Hematology·Silvia ColucciSandro Altamura

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