Defective bone morphogenic protein signaling underlies hepcidin deficiency in HFE hereditary hemochromatosis

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
John D RyanJohn Crowe

Abstract

Hereditary hemochromatosis (HH) is a common inherited iron overload disorder. The vast majority of patients carry the missense Cys282Tyr mutation of the HFE gene. Hepcidin, the central regulator of iron homeostasis, is deficient in HH, leading to unchecked iron absorption and subsequent iron overload. The bone morphogenic protein (BMP)/small mothers against decapentaplegic (Smad) signaling cascade is central to the regulation of hepcidin. Recent data from HH mice models indicate that this pathway may be defective in the absence of the HFE protein. Hepatic BMP/Smad signaling has not been characterized in a human HFE-HH cohort to date. Hepatic expression of BMP/Smad-related genes was examined in 20 HFE-HH males with significant iron overload, and compared to seven male HFE wild-type controls using quantitative real-time reverse transcription polymerase chain reaction. Hepatic expression of BMP6 was appropriately elevated in HFE-HH compared to controls (P = 0.02), likely related to iron overload. Despite this, no increased expression of the BMP target genes hepcidin and Id1 was observed, and diminished phosphorylation of Smad1/Smad5/Smad8 protein relative to iron burden was found upon immunohistochemical analysis, suggesting that ...Continue Reading

References

Jan 1, 1986·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M L BassettL W Powell
Jan 1, 1993·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y M DeugnierJ W Halliday
Aug 1, 1996·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·P Bedossa, T Poynard
Sep 26, 1997·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K HouglumM Chojkier
Oct 23, 1997·Nature·T ImamuraK Miyazono
Aug 26, 1998·Biochemical and Biophysical Research Communications·M AfrakhteP ten Dijke
Dec 23, 1999·The New England Journal of Medicine·N C Andrews
May 8, 2001·The Journal of Nutrition·M D KnutsonM Wessling-Resnick
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Aug 23, 2002·European Journal of Clinical Investigation·A LebeauK Schümann
Jan 28, 2003·Blood Cells, Molecules & Diseases·Kaashif A AhmadRobert E Fleming
Jul 10, 2003·Gastroenterology·Steven DooleyAxel M Gressner
Jun 4, 2004·The New England Journal of Medicine·Antonello Pietrangelo
Jun 12, 2004·Proceedings of the National Academy of Sciences of the United States of America·Pauline LeeErnest Beutler
Aug 19, 2004·European Journal of Gastroenterology & Hepatology·F GleesonJ Crowe
Feb 18, 2005·Journal of Biochemistry and Molecular Biology·Seok Hee Park
Apr 11, 2006·Nature Genetics·Jodie L BabittHerbert Y Lin
Feb 1, 2007·Blood·Maja Vujic SpasicMartina U Muckenthaler
Feb 24, 2007·Current Opinion in Cell Biology·Susumu Itoh, Peter ten Dijke
Jul 4, 2007·The Journal of Clinical Investigation·Jodie L BabittHerbert Y Lin
Aug 29, 2007·Blood·Alberto PipernoClara Camaschella
Dec 7, 2007·Lancet·Paul C Adams, James C Barton
Feb 6, 2008·Cell Metabolism·Maja Vujić SpasićMartina U Muckenthaler
Mar 5, 2008·Cell Metabolism·Paul J SchmidtNancy C Andrews
Apr 19, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Maria Vittoria Verga FalzacappaMartina U Muckenthaler
Jul 2, 2008·Cell Metabolism·Martina U Muckenthaler
Mar 3, 2009·Nature Genetics·Billy AndriopoulosJodie L Babitt
Mar 3, 2009·Nature Genetics·Delphine MeynardMarie-Paule Roth
Apr 2, 2009·Nature Genetics·Clara Camaschella
Dec 31, 2009·Blood·Katarzyna Mleczko-SaneckaMartina U Muckenthaler

❮ Previous
Next ❯

Citations

Feb 26, 2011·Inflammatory Bowel Diseases·Lijian WangBobby J Cherayil
Aug 1, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alina DabaKostas Pantopoulos
Jul 9, 2011·The British Journal of Nutrition·Natsumi IshizakiTohru Matsui
Jun 19, 2012·Biochemistry·Kostas PantopoulosL Devireddy
Aug 1, 1995·Journal of Advanced Nursing·L Land
Nov 10, 2012·Science·Hal Drakesmith, Andrew M Prentice
Aug 7, 2013·Nutrients·Andrea U Steinbicker, Martina U Muckenthaler
Aug 29, 2013·World Journal of Gastroenterology : WJG·Catherine M GreeneMatthew W Lawless
Nov 16, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Kimberly Zumbrennen-Bullough, Jodie L Babitt
Jul 6, 2014·Annual Review of Nutrition·Nermi L Parrow, Robert E Fleming
Sep 9, 2011·Metallomics : Integrated Biometal Science·Giada Sebastiani, Kostas Pantopoulos
Oct 26, 2013·The American Journal of the Medical Sciences·Cindy N Roy
Sep 25, 2010·Blood Cells, Molecules & Diseases·Giuliano BolondiAntonello Pietrangelo
Sep 12, 2015·Scientific Reports·Justin B GohV Nathan Subramaniam
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
Jul 12, 2011·American Journal of Medical Genetics. Part a·Jill A RosenfeldLisa G Shaffer
Sep 11, 2012·Biochimica Et Biophysica Acta·Maja Vujić SpasićMartina U Muckenthaler
Jan 23, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Patricia KentKostas Pantopoulos
Aug 26, 2014·Blood·Martina U Muckenthaler
Nov 10, 2013·Blood·Delphine MeynardHerbert Y Lin
Mar 22, 2014·Frontiers in Pharmacology·Maja Vujić
Nov 8, 2018·Blood·Chia-Yu Wang, Jodie L Babitt
Dec 19, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Samer Chehade, Paul C Adams
May 28, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Chia-Yu WangJodie L Babitt
Nov 30, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xia XiaoJodie L Babitt
Dec 24, 2010·Journal of Clinical Pathology·Manuel MuñozAngel Francisco Remacha
Jul 17, 2015·Bioscience Reports·Gautam RishiV Nathan Subramaniam
Nov 29, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Cameron J McDonaldV Nathan Subramaniam
Nov 14, 2018·Frontiers in Nutrition·Kostas Pantopoulos
Apr 30, 2016·The Journal of Biological Chemistry·Simeng ChenMartina U Muckenthaler
Dec 5, 2018·Nature Microbiology·Lucy A EddowesHal Drakesmith
May 1, 2021·Biochemical Society Transactions·Márcio Simão, M Leonor Cancela
May 25, 2021·Hepatology Communications·Kris V KowdleyPriya Handa
May 17, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Allison L Fisher, Jodie L Babitt

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