BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism

Blood

Volumn 124, Issue 13, 2014, Pages 2116-2123

  Mayeur, Claire ^a   Leyton, Patricio A ^a   Kolodziej, Starsha A ^a   Yu, Binglan ^a   Bloch, Kenneth D ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN 6; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; HEPCIDIN; IRON; MESSENGER RNA; TATA BINDING PROTEIN; TRANSFERRIN RECEPTOR; ACTIN RELATED PROTEIN 2;

ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; FEMALE; GENE CONTROL; GENE EXPRESSION; HUMAN; HUMAN CELL; IRON METABOLISM; IRON OVERLOAD; LIVER CELL; MOUSE; NONHUMAN; PROTEIN BLOOD LEVEL; ANIMAL; DEFICIENCY; GENE DELETION; GENE EXPRESSION REGULATION; GENETICS; HETEROZYGOTE; KNOCKOUT MOUSE; LIVER; METABOLISM; MUTATION; PATHOLOGY; SIGNAL TRANSDUCTION;

ACTIN-RELATED PROTEIN 2; ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; FEMALE; GENE DELETION; GENE EXPRESSION REGULATION; HEPATOCYTES; HEPCIDINS; HETEROZYGOTE; HUMANS; IRON; IRON OVERLOAD; LIVER; MICE; MICE, KNOCKOUT; MUTATION; RNA, MESSENGER; SIGNAL TRANSDUCTION;

EID: 84907266506     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-04-572644     Document Type: Article

References (40)

1. Ganz T. Systemic iron homeostasis. Physiol Rev. 2013; 93(4):1721-1741.
2. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004; 306(5704):2090-2093.
3. Finberg KE, Heeney MM, Campagna DR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet. 2008; 40(5):569-571.
4. Lesbordes-Brion JC, Viatte L, Bennoun M, et al. Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis. Blood. 2006; 108(4): 1402-1405.
5. Zumerle S, Mathieu JR, Delga S, et al. Targeted disruption of hepcidin in the liver recapitulates the hemochromatotic phenotype. Blood. 2014; 123(23):3646-3650.
6. Evstatiev R, Gasche C. Iron sensing and signalling. Gut. 2012; 61(6):933-952.
7. Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006; 38(5):531-539.
8. Babitt JL, Huang FW, Xia Y, Sidis Y, Andrews NC, Lin HY. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest. 2007; 117(7):1933-1939.
9. Andriopoulos B Jr, Corradini E, Xia Y, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet. 2009; 41(4):482-487.
10. Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet. 2009; 41(4):478-481.
11. Wu Q, Sun CC, Lin HY, Babitt JL. Repulsive guidance molecule (RGM) family proteins exhibit differential binding kinetics for bone morphogenetic proteins (BMPs). PLoS ONE. 2012; 7(9):e46307.
12. Miyazono K, Kamiya Y, Morikawa M. Bone morphogenetic protein receptors and signal transduction. J Biochem. 2010; 147(1):35-51.
13. Steinbicker AU, Bartnikas TB, Lohmeyer LK, et al. Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice. Blood. 2011; 118(15):4224-4230.
14. National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health. UniGene. http://www.ncbi.nlm.nih.gov/unigene. Accessed April 22, 2014.
15. Rhodes CJ, Howard LS, Busbridge M, et al. Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension: clinical prevalence, outcomes, and mechanistic insights. J Am Coll Cardiol. 2011; 58(3):300-309.
16. Xia Y, Babitt JL, Sidis Y, Chung RT, Lin HY. Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood. 2008; 111(10): 5195-5204.
17. Ruiter G, Lankhorst S, Boonstra A, et al. Iron deficiency is common in idiopathic pulmonary arterial hypertension. Eur Respir J. 2011; 37(6): 1386-1391.
18. Soon E, Treacy CM, Toshner MR, et al. Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension. Thorax. 2011; 66(4):326-332.
19. van Empel VP, Lee J, Williams TJ, Kaye DM. Iron deficiency in patients with idiopathic pulmonary arterial hypertension. Heart Lung Circ. 2014; 23(3):287-292.
20. Morrell NW. Pulmonary hypertension due to BMPR2 mutation: a new paradigm for tissue remodeling? Proc Am Thorac Soc. 2006; 3(8): 680-686.
21. Beppu H, Ichinose F, Kawai N, et al. BMPR-II heterozygous mice have mild pulmonary hypertension and an impaired pulmonary vascular remodeling response to prolonged hypoxia. Am J Physiol Lung Cell Mol Physiol. 2004; 287(6): L1241-L1247.
22. Beppu H, Kawabata M, Hamamoto T, et al. BMP type II receptor is required for gastrulation and early development of mouse embryos. Dev Biol. 2000; 221(1):249-258.
23. Beppu H, Lei H, Bloch KD, Li E. Generation of a floxed allele of the mouse BMP type II receptor gene. Genesis. 2005; 41(3):133-137.
24. Song J, Oh SP, Schrewe H, et al. The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice. Dev Biol. 1999; 213(1): 157-169.
25. Izamis M-L, Calhoun C, Uygun BE, et al. Simple Machine Perfusion Significantly Enhances Hepatocyte Yields of Ischemic and Fresh Rat Livers. Cell Medicine. 2013; 4(3):109-123.
26. Atkinson C, Stewart S, Upton PD, et al. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation. 2002; 105(14):1672-1678.
27. Kautz L, Besson-Fournier C, Meynard D, Latour C, Roth MP, Coppin H. Iron overload induces BMP6 expression in the liver but not in the duodenum. Haematologica. 2011; 96(2):199-203.
28. Yu PB, Hong CC, Sachidanandan C, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008; 4(1):33-41.
29. Bagarova J, Vonner AJ, Armstrong KA, et al. Constitutively active ALK2 receptor mutants require type II receptor cooperation. Mol Cell Biol. 2013; 33(12):2413-2424.
30. Yu PB, Beppu H, Kawai N, Li E, Bloch KD. Bone morphogenetic protein (BMP) type II receptor deletion reveals BMP ligand-specific gain of signaling in pulmonary artery smooth muscle cells. J Biol Chem. 2005; 280(26):24443-24450.
31. Mayeur C, Lohmeyer LK, Leyton P, et al. The type I BMP receptor Alk3 is required for the induction of hepatic hepcidin gene expression by interleukin-6. Blood. 2014; 123(14):2261-2268.
32. Dussiot M, Maciel TT, Fricot A, et al. An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia. Nat Med. 2014; 20(4):398-407.
33. Ramos E, Kautz L, Rodriguez R, et al. Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice. Hepatology. 2011; 53(4):1333-1341.
34. Greenwald J, Groppe J, Gray P, et al. The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly. Mol Cell. 2003; 11(3):605-617.
35. Leyton PA, Beppu H, Pappas A, et al. Deletion of the sequence encoding the tail domain of the bone morphogenetic protein type 2 receptor reveals a bone morphogenetic protein 7-specific gain of function. PLoS ONE. 2013; 8(10):e76947.
36. Besson-Fournier C, Latour C, Kautz L, et al. Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling. Blood. 2012; 120(2):431-439.
37. Lavery K, Swain P, Falb D, Alaoui-Ismaili MH. BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J Biol Chem. 2008; 283(30):20948-20958.
38. Upton PD, Davies RJ, Trembath RC, Morrell NW. Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells. J Biol Chem. 2009; 284(23):15794-15804.
39. Han R, Beppu H, Lee YK, et al. A pair of transmembrane receptors essential for the retention and pigmentation of hair. Genesis. 2012; 50(11):783-800.
40. Little SC, Mullins MC. Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis. Nat Cell Biol. 2009; 11(5):637-643.