Iron-Induced Expression of Bone Morphogenic Protein 6 in Intestinal Cells Is the Main Regulator of Hepatic Hepcidin Expression In Vivo

Gastroenterology

Volumn 138, Issue 1, 2010, Pages 372-382

  Arndt, Stephanie ^a   Maegdefrau, Ulrike ^a   Dorn, Christoph ^a   Schardt, Katharina ^a   Hellerbrand, Claus ^a   Bosserhoff, Anja Katrin ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; BONE MORPHOGENETIC PROTEIN 6; BONE MORPHOGENETIC PROTEIN 9; BONE MORPHOGENETIC PROTEIN RECEPTOR; FERROUS SULFATE; HEPCIDIN; IRON; RECEPTOR SUBUNIT; TRANSFERRIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BIOACCUMULATION; CONTROLLED STUDY; DIET SUPPLEMENTATION; EPITHELIUM CELL; EX VIVO STUDY; FEMALE; IN VITRO STUDY; IN VIVO STUDY; INTESTINE CELL; IRON METABOLISM; IRON OVERLOAD; LIVER CELL; MACROPHAGE; MALE; MOLECULAR MECHANICS; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INDUCTION; SMALL INTESTINE; UPREGULATION;

EID: 72249109128     PISSN: 00165085     EISSN: None     Source Type: Journal    
DOI: 10.1053/j.gastro.2009.09.048     Document Type: Article

References (29)

1. Lee P., Peng H., Gelbart T., et al. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci U S A 102 (2005) 1906-1910
2. Nemeth E., Rivera S., Gabayan V., et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113 (2004) 1271-1276
3. Hentze M.W., Muckenthaler M.U., and Andrews N.C. Balancing acts: molecular control of mammalian iron metabolism. Cell 117 (2004) 285-297
4. Pietrangelo A. Hereditary hemochromatosis. Biochim Biophys Acta 1763 (2006) 700-710
5. Roetto A., Papanikolaou G., Politou M., et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33 (2003) 21-22
6. Weiss G., and Gordeuk V.R. Benefits and risks of iron therapy for chronic anaemias. Eur J Clin Invest 35 Suppl 3 (2005) 36-45
7. Weiss G., and Goodnough L.T. Anemia of chronic disease. N Engl J Med 352 (2005) 1011-1023
8. Babitt J.L., Huang F.W., Wrighting D.M., et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 38 (2006) 531-539
9. Babitt J.L., Huang F.W., Xia Y., et al. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest 117 (2007) 1933-1939
10. Wang R.H., Li C., Xu X., et al. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab 2 (2005) 399-409
11. Meynard D., Kautz L., Darnaud V., et al. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet 41 (2009) 478-481
12. Andriopoulos Jr. B., Corradini E., Xia Y., et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet 41 (2009) 482-487
13. Solloway M.J., Dudley A.T., Bikoff E.K., et al. Mice lacking Bmp6 function. Dev Genet 22 (1998) 321-339
14. Muhlbauer M., Fleck M., Schutz C., et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-α and -γ and mediates T-cell apoptosis. J Hepatol 45 (2006) 520-528
15. Hellerbrand C., Bosserhoff A.K., Seegers S., et al. Mutation analysis of the HFE gene in German hemochromatosis patients and controls using automated SSCP-based capillary electrophoresis and a new PCR-ELISA technique. Scand J Gastroenterol 36 (2001) 1211-1216
16. Arndt S., and Bosserhoff A.K. Reduced expression of TANGO in colon and hepatocellular carcinomas. Oncol Rep 18 (2007) 885-891
17. Kirsch R., Sijtsema H.P., Tlali M., et al. Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease. Liver Int 26 (2006) 1258-1267
18. Edison E.S., Bajel A., and Chandy M. Iron homeostasis: new players, newer insights. Eur J Haematol 81 (2008) 411-424
19. Batts K.P. Iron overload syndromes and the liver. Mod Pathol 20 Suppl 1 (2007) S31-S39
20. Kautz L., Meynard D., Monnier A., et al. Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver. Blood 112 (2008) 1503-1509
21. Truksa J., Peng H., Lee P., et al. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci U S A 103 (2006) 10289-10293
22. Yu P.B., Hong C.C., Sachidanandan C., et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 4 (2008) 33-41
23. Aoki H., Fujii M., Imamura T., et al. Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction. J Cell Sci 114 (2001) 1483-1489
24. Derynck R., and Zhang Y.E. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature 425 (2003) 577-584
25. Rodriguez A., Hilvo M., Kytomaki L., et al. Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse. BMC Genomics 8 (2007) 379
26. Courselaud B., Troadec M.B., Fruchon S., et al. Strain and gender modulate hepatic hepcidin 1 and 2 mRNA expression in mice. Blood Cells Mol Dis 32 (2004) 283-289
27. Saremba S., Nickel J., Seher A., et al. Type I receptor binding of bone morphogenetic protein 6 is dependent on N-glycosylation of the ligand. FEBS J 275 (2008) 172-183
28. Gitelman S.E., Kobrin M.S., Ye J.Q., et al. Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo. J Cell Biol 126 (1994) 1595-1609
29. Scheuer P.J., Williams R., and Muir A.R. Hepatic pathology in relatives of patients with haemochromatosis. J Pathol Bacteriol 84 (1962) 53-64