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Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance
Open accessAbstract
Systemic iron balance is regulated by hepcidin, a peptide hormone secreted by the liver.By decreasing cell surface expression of the iron exporter ferroportin, hepcidin decreases iron absorption from the intestine and iron release from reticuloendothelial stores.Hepcidin excess has been implicated in the pathogenesis of anemia of chronic disease, while hepcidin deficiency has a key role in the pathogenesis of the iron overload disorder hemochromatosis.We have recently shown that hemojuvelin is a coreceptor for bone morphogenetic protein (BMP) signaling and that BMP signaling positively regulates hepcidin expression in liver cells in vitro.Here we show that BMP-2 administration increases hepcidin expression and decreases serum iron levels in vivo.We also show that soluble hemojuvelin (HJV.Fc) selectively inhibits BMP induction of hepcidin expression in vitro and that administration of HJV.Fc decreases hepcidin expression, increases ferroportin expression, mobilizes splenic iron stores, and increases serum iron levels in vivo.These data support a role for modulators of the BMP signaling pathway in treating diseases of iron overload and anemia of chronic disease.Nonstandard abbreviations used: BMP, bone morphogenetic protein; GDF, growth and differentiation factor; HJV.Fc, soluble hemojuvelin comprised of the extracellular domain of hemojuvelin fused to the Fc portion of human IgG; pRL-TK, Renilla luciferase vector.
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Cites
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803
Weiss, G., & Goodnough, L. T. (2005) · New England Journal of Medicine · doi:10.1056/nejmra041809 · Cited by 3,800
Nemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420945 · Cited by 2,650
Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736
Self-citationPigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697
LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity
Krause, A., Neitz, S., Mägert, H.-J., Schulz, A., Forssmann, W.-G., Schulz-Knappe, P., & Adermann, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01920-7 · Cited by 1,324
Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression
Babitt, J. L., Huang, F. W., Wrighting, D. M., Xia, Y., Sidis, Y., Samad, T. A., Campagna, J. A., Chung, R. T., Schneyer, A. L., Woolf, C. J., et al. (2006) · Nature Genetics · doi:10.1038/ng1777 · Cited by 1,026
Interleukin-6 induces hepcidin expression through STAT3
Wrighting, D. M., & Andrews, N. C. (2006) · Blood · doi:10.1182/blood-2006-06-027631 · Cited by 983
Self-citationMutations in HFE2 cause iron overload in chromosome 1q–linked juvenile hemochromatosis
Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L. E., Franchini, P. L., Dubé, M.-P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., et al. (2004) · Nature Genetics · doi:10.1038/ng1274 · Cited by 974
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Weiss, G., & Goodnough, L. T. (2005) · New England Journal of Medicine · doi:10.1056/nejmra041809 · Cited by 3,800
Ganz, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2013 · Cited by 1,122
Hepcidin and iron regulation, 10 years later
Ganz, T. (2011) · Blood · doi:10.1182/blood-2011-01-258467 · Cited by 962
BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism
Andriopoulos Jr, B., Corradini, E., Xia, Y., Faasse, S. A., Chen, S., Grgurevic, L., Knutson, M. D., Pietrangelo, A., Vukicevic, S., Lin, H. Y., et al. (2009) · Nature Genetics · doi:10.1038/ng.335 · Cited by 769
Self-citationHereditary Hemochromatosis: Pathogenesis, Diagnosis, and Treatment
Pietrangelo, A. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.06.013 · Cited by 615
Forging a field: the golden age of iron biology.
Andrews, N. C. (2008) · Blood · doi:10.1182/blood-2007-12-077388 · Cited by 623
Self-citationMechanisms of mammalian iron homeostasis
Pantopoulos, K., Porwal, S. K., Tartakoff, A., & Devireddy, L. (2012) · Biochemistry · doi:10.1021/bi300752r · Cited by 598
Lack of the bone morphogenetic protein BMP6 induces massive iron overload
Meynard, D., Kautz, L., Darnaud, V., Canonne-Hergaux, F., Coppin, H., & Roth, M.-P. (2009) · Nature Genetics · doi:10.1038/ng.320 · Cited by 587
Silvestri, L., Pagani, A., Nai, A., De Domenico, I., Kaplan, J., & Camaschella, C. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.012 · Cited by 555
Regulation of iron transport and the role of transferrin
Gkouvatsos, K., Papanikolaou, G., & Pantopoulos, K. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.10.013 · Cited by 518
Intracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526
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Wessling-Resnick, M. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104804 · Cited by 480
Regulation of iron acquisition and storage: consequences for iron-linked disorders
De Domenico, I., McVey Ward, D., & Kaplan, J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2295 · Cited by 464
Hepcidin and disorders of iron metabolism
Ganz, T., & Nemeth, E. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-050109-142444 · Cited by 466
Kautz, L., Meynard, D., Monnier, A., Darnaud, V., Bouvet, R., Wang, R.-H., Deng, C., Vaulont, S., Mosser, J., Coppin, H., et al. (2008) · Blood · doi:10.1182/blood-2008-03-143354 · Cited by 437
Shah, Y. M., Matsubara, T., Ito, S., Yim, S.-H., & Gonzalez, F. J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.012 · Cited by 431
Iron Sequestration and Anemia of Inflammation
Ganz, T., & Nemeth, E. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2009.06.001 · Cited by 361
Liver iron sensing and body iron homeostasis
Wang, C.-Y., & Babitt, J. L. (2019) · Blood · doi:10.1182/blood-2018-06-815894 · Cited by 360
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Weiss, G. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.08.006 · Cited by 322
Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis
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Jiao, Y., Wilkinson, J., Di, X., Wang, W., Hatcher, H., Kock, N. D., D'Agostino, R., Knovich, M. A., Torti, F. M., & Torti, S. V. (2009) · Blood · doi:10.1182/blood-2008-05-155952 · Cited by 266
Hepcidin in Human Iron Disorders: Diagnostic Implications
Kroot, J. J., Tjalsma, H., Fleming, R. E., & Swinkels, D. W. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2009.140053 · Cited by 246
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Portugal, S., Carret, C., Recker, M., Armitage, A. E., Gonçalves, L. A., Epiphanio, S., Sullivan, D., Roy, C., Newbold, C. I., Drakesmith, H., et al. (2011) · Nature Medicine · doi:10.1038/nm.2368 · Cited by 232
Song, S.-N. J., Tomosugi, N., Kawabata, H., Ishikawa, T., Nishikawa, T., & Yoshizaki, K. (2010) · Blood · doi:10.1182/blood-2010-03-271791 · Cited by 228
Hepcidin: regulation of the master iron regulator
Rishi, G., Wallace, D. F., & Subramaniam, V. N. (2015) · Bioscience Reports · doi:10.1042/bsr20150014 · Cited by 223
Ginzburg, Y., & Rivella, S. (2011) · Blood · doi:10.1182/blood-2011-03-283614 · Cited by 201
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Nickel, J., Ten Dijke, P., & Mueller, T. D. (2018) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmx126 · Cited by 198
The Role of Iron in the Immune Response to Bacterial Infection
Cherayil, B. J. (2011) · Immunologic Research · doi:10.1007/s12026-010-8199-1 · Cited by 191
Corradini, E., Meynard, D., Wu, Q., Chen, S., Ventura, P., Pietrangelo, A., & Babitt, J. L. (2011) · Hepatology · doi:10.1002/hep.24359 · Cited by 194
Self-citationPharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats
Theurl, I., Schroll, A., Sonnweber, T., Nairz, M., Theurl, M., Willenbacher, W., Eller, K., Wolf, D., Seifert, M., Sun, C. C., et al. (2011) · Blood · doi:10.1182/blood-2011-03-345066 · Cited by 189
Self-citationBesson-Fournier, C., Latour, C., Kautz, L., Bertrand, J., Ganz, T., Roth, M.-P., & Coppin, H. (2012) · Blood · doi:10.1182/blood-2012-02-411470 · Cited by 179
Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation
Steinbicker, A. U., Sachidanandan, C., Vonner, A. J., Yusuf, R. Z., Deng, D. Y., Lai, C. S., Rauwerdink, K. M., Winn, J. C., Saez, B., Cook, C. M., et al. (2011) · Blood · doi:10.1182/blood-2010-10-313064 · Cited by 173
The Hepcidin-Ferroportin System as a Therapeutic Target in Anemias and Iron Overload Disorders
Ganz, T., & Nemeth, E. (2011) · Hematology · doi:10.1182/asheducation-2011.1.538 · Cited by 172
Review article: the iron overload syndromes
Siddique, A., & Kowdley, K. V. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2012.05051.x · Cited by 162
Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice
Wang, L., Harrington, L., Trebicka, E., Shi, H. N., Kagan, J. C., Hong, C. C., Lin, H. Y., Babitt, J. L., & Cherayil, B. J. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39939 · Cited by 162
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Poli, M., Girelli, D., Campostrini, N., Maccarinelli, F., Finazzi, D., Luscieti, S., Nai, A., & Arosio, P. (2011) · Blood · doi:10.1182/blood-2010-06-289082 · Cited by 148
Verga Falzacappa, M. V., Casanovas, G., Hentze, M. W., & Muckenthaler, M. U. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-008-0313-7 · Cited by 146
In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2
Maes, K., Nemeth, E., Roodman, G. D., Huston, A., Esteve, F., Freytes, C., Callander, N., Katodritou, E., Tussing-Humphreys, L., Rivera, S., et al. (2010) · Blood · doi:10.1182/blood-2010-03-274571 · Cited by 132
Bone morphogenetic protein 2 controls iron homeostasis in mice independent of Bmp6
Canali, S., Wang, C., Zumbrennen‐Bullough, K. B., Bayer, A., & Babitt, J. L. (2017) · American Journal of Hematology · doi:10.1002/ajh.24888 · Cited by 133
Self-citationHepcidin antagonists for potential treatments of disorders with hepcidin excess
Poli, M., Asperti, M., Ruzzenenti, P., Regoni, M., & Arosio, P. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00086 · Cited by 124
Iron and innate antimicrobial immunity-depriving the pathogen, defending the host
Nairz, M., Dichtl, S., Schroll, A., Haschka, D., Tymoszuk, P., Theurl, I., & Weiss, G. (2018) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2018.03.007 · Cited by 123
Canali, S., Core, A. B., Zumbrennen-Bullough, K. B., Merkulova, M., Wang, C.-Y., Schneyer, A. L., Pietrangelo, A., & Babitt, J. L. (2016) · Endocrinology · doi:10.1210/en.2015-1747 · Cited by 113
Self-citationAnemia of chronic disorders: new diagnostic tools and new treatment strategies
Weiss, G. (2015) · Seminars in Hematology · doi:10.1053/j.seminhematol.2015.07.004 · Cited by 116
Progesterone receptor membrane component-1 regulates hepcidin biosynthesis
Li, X., Rhee, D. K., Malhotra, R., Mayeur, C., Hurst, L. A., Ager, E., Shelton, G., Kramer, Y., McCulloh, D., Keefe, D., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci83831 · Cited by 112
Corradini, E., Schmidt, P. J., Meynard, D., Garuti, C., Montosi, G., Chen, S., Vukicevic, S., Pietrangelo, A., Lin, H. Y., & Babitt, J. L. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.07.044 · Cited by 109
Self-citationNai, A., Rubio, A., Campanella, A., Gourbeyre, O., Artuso, I., Bordini, J., Gineste, A., Latour, C., Besson-Fournier, C., Lin, H. Y., et al. (2016) · Blood · doi:10.1182/blood-2015-11-681494 · Cited by 97
Self-citationIron-Sensing Proteins that Regulate Hepcidin and Enteric Iron Absorption
Knutson, M. D. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104801 · Cited by 96
Regulation of growth differentiation factor 15 expression by intracellular iron
Lakhal, S., Talbot, N. P., Crosby, A., Stoepker, C., Townsend, A. R. M., Robbins, P. A., Pugh, C. W., Ratcliffe, P. J., & Mole, D. R. (2009) · Blood · doi:10.1182/blood-2008-07-170431 · Cited by 95
Volke, M., Gale, D. P., Maegdefrau, U., Schley, G., Klanke, B., Bosserhoff, A.-K., Maxwell, P. H., Eckardt, K.-U., & Warnecke, C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007875 · Cited by 93
Genetic mechanisms and modifying factors in hereditary hemochromatosis
Weiss, G. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2009.201 · Cited by 82
Mayeur, C., Leyton, P. A., Kolodziej, S. A., Yu, B., & Bloch, K. D. (2014) · Blood · doi:10.1182/blood-2014-04-572644 · Cited by 74
Enns, C. A., Ahmed, R., Wang, J., Ueno, A., Worthen, C., Tsukamoto, H., & Zhang, A.-S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060534 · Cited by 69
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Leclère, L., & Rentzsch, F. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.11.009 · Cited by 67
Function of the hemochromatosis protein HFE: Lessons from animal models
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Frazer, D. M., Wilkins, S. J., Darshan, D., Badrick, A. C., McLaren, G. D., & Anderson, G. J. (2012) · British Journal of Haematology · doi:10.1111/j.1365-2141.2012.09104.x · Cited by 43
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Wu, X., Yung, L.-M., Cheng, W.-H., Yu, P. B., Babitt, J. L., Lin, H. Y., & Xia, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044622 · Cited by 34
Self-citationNormal systemic iron homeostasis in mice with macrophage-specific deletion of transferrin receptor 2
Rishi, G., Secondes, E. S., Wallace, D. F., & Subramaniam, V. N. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00291.2015 · Cited by 21
High sulfation and a high molecular weight are important for anti-hepcidin activity of heparin
Asperti, M., Naggi, A., Esposito, E., Ruzzenenti, P., Di Somma, M., Gryzik, M., Arosio, P., & Poli, M. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00316 · Cited by 17
Metadata
- Authors
- Babitt, J. L., Huang, F. W., Xia, Y., Sidis, Y., Andrews, N. C., & Lin, H. Y.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-07-02
- Volume
- 117
- Issue
- 7
- Pages
- 1933-1939
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2117133328
- Cited by
- 457
- References
- 16
- FWCI
- 28.94
- Type
- journal article
- Language
- en
- Open access
- bronze
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