The DOI matches its Crossref record; 50 of the 52 references it cites were found in a registry or an index.
Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression
Abstract
Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency induces iron overload, whereas hepcidin excess induces anemia. Mutations in the gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload and correlate with low hepcidin levels, suggesting that hemojuvelin positively regulates hepcidin expression. Hemojuvelin is a member of the repulsive guidance molecule (RGM) family, which also includes the bone morphogenetic protein (BMP) coreceptors RGMA and DRAGON (RGMB). Here, we report that hemojuvelin is a BMP coreceptor and that hemojuvelin mutants associated with hemochromatosis have impaired BMP signaling ability. Furthermore, BMP upregulates hepatocyte hepcidin expression, a process enhanced by hemojuvelin and blunted in Hfe2-/- hepatocytes. Our data suggest a mechanism by which HFE2 mutations cause hemochromatosis: hemojuvelin dysfunction decreases BMP signaling, thereby lowering hepcidin expression.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The latter is due to the fact, that several co-factors expressed on the hepatocyte cell membrane such as HFE, hemojuvelin (HJV) or TfR2 impact on hepcidin expression via the BMP-SMAD pathway (Babitt et al., 2006).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Babitt et al., 2006
In the citing paper
“Regulation of hepcidin by iron depends on the hemojuvelin (HJV) and bone morphogenetic protein receptor (BMPR) complex activating the SMAD signaling pathway (Fig 3) [13–15].”
From Hepcidin and Host Defense against Infectious Diseases (2015) · cites this paper as [13]
In the citing paper
“HJV is a BMP co-receptor that enhances iron signaling to hepcidin (Babitt et al., 2006).”
From Pharmacological Targeting of the Hepcidin/Ferroportin Axis (2016) · cites this paper as Babitt et al., 2006
In the citing paper
“BMP6 binds to a heterodimeric receptor complexed with hemojuvelin (HJV) and matriptase-2 (the gene product of TMPRSS6), and stimulates HAMP expression [66, 67].”
From Iron deficiency or anemia of inflammation?: Differential diagnosis and mechanisms of anemia of inflammation (2016) · cites this paper as [67]
In the citing paper
“Nonetheless, BMP treatment is a potent stimulus for hepcidin expression both in cultured cells 113,114,116,117 and in animals.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [114]
In the citing paper
“They showed that hemojuvelin acts as a BMP coreceptor to stimulate hepcidin transcription.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [114]
In the citing paper
“Activation of signaling through the hemochromatosis protein HFE, TFR1, TFR2, or hemojuvelin (HJV), which acts as a co-receptor for bone morphogenetic protein 6 (BMP6), increases hepcidin transcription in a SMAD-dependent fashion.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [200]
In the citing paper
“HFE2 is a BMP coreceptor, and its mutation suppresses BMP signaling (14).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [14]
In the citing paper
“An alternative mechanism of hepcidin regulation through a signaling pathway involving hemojuvelin (HFE2, also known as HJV) and bone morphogenetic proteins (BMP) was recently identified (14).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [14]
In the citing paper
“This study showed that BMP could upregulate hepcidin in hepatocytes.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [14]
In the citing paper
“hepatocytes deficient in HFE2 had impaired hepcidin induction by BMP signaling (14).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [14]
In the citing paper
“Overexpression of HFE2 enhanced hepcidin production.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [14]
In the citing paper
“Smad4-knockout mice had lower levels of hepcidin and did not induce hepcidin in response to iron loading or IL-6 stimulation (14).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [14]
In the citing paper
“downstream activation of Smad4 was required for BMP-mediated hepcidin upregulation,”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [14]
Citations
Cites
Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus
Shi, Y., & Massagué, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00432-x · Cited by 5,860
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
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
Bone morphogenetic proteins: multifunctional regulators of vertebrate development.Preprint
Hogan, B. L. M. (1996) · Genes & Development · doi:10.1101/gad.10.13.1580 · Cited by 1,964
Dennler, S., Itoh, S., Vivien, D., ten Dijke, P., Huet, S., & Gauthier, J. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3091 · Cited by 1,793
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
Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
Nemeth, E., Valore, E. V., Territo, M., Schiller, G., Lichtenstein, A., & Ganz, T. (2003) · Blood · doi:10.1182/blood-2002-10-3235 · Cited by 1,417
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
Flagged first, then by citations
2 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 701–800 of 999
Runx3 regulates iron metabolism via modulation of BMP signalling
Kim, H., Lee, J., Lee, Y., Li, S., Lee, S., Bae, S., & Jung, H.-S. (2021) · Cell Proliferation · doi:10.1111/cpr.13138 · Cited by 11
Zheng, H., Yang, F., Deng, K., Wei, J., Liu, Z., Zheng, Y., & Xu, H. (2023) · Medicine · doi:10.1097/md.0000000000033225 · Cited by 12
“BMPs represent a large subfamily of the transforming growth factor b ligand superfamily, which shares a common signal transduction model.[13] The BMP subfamily regulates hepcidin expression by signaling through receptor-activated Smads.”
BackgroundCrystal structure of a hemojuvelin-binding fragment of neogenin at 1.8Å
Yang, F., West, A. P., & Björkman, P. J. (2010) · Journal of Structural Biology · doi:10.1016/j.jsb.2010.10.005 · Cited by 12
“The discovery of hemojuvelin as a co-receptor for BMP during activation of hepcidin expression (Babitt et al., 2006) suggested the possibility of using BMP antagonists for the treatment of anemia (Browne and Reddan, 2009).”
BackgroundOnofre, C., Tomé, F., Barbosa, C., Silva, A. L., & Romão, L. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.01462-14 · Cited by 12
“Due to this process, HJV expression leads to an increase in hepcidin expression, demonstrating its fundamental role in systemic iron metabolism (22, 25).”
BackgroundAnti-mouse CD52 monoclonal antibody ameliorates iron-deficient anaemia in IL-10 knockout mice
Wang, H., Dong, J., Zuo, L., Liu, J., Zhu, W., Li, Y., Gu, L., Zhao, J., Zhang, L., Gong, J., et al. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114513003413 · Cited by 12
“reported that BMP 6 induces hepcidin expression by activating Smad1/5/8, which is in line with another study showing that haemojuvelin, a glycosyl-phosphatidyl-inositol-linked membrane-associated protein, binds to BMP and enhances their effectiveness to activate the BMP–SMAD signalling pathway to stimulate hepcidin tr…”
ResultKim, D., Kim, Y., Jung, Y. S., Kim, K.-S., Jeong, J., Lee, Y.-S., Yuk, J., Oh, B., Choy, H. E., Dooley, S., et al. (2016) · Scientific Reports · doi:10.1038/srep34630 · Cited by 12
Advances in understanding the crosstalk between mother and fetus on iron utilization
Lakhal‐Littleton, S. (2021) · Seminars in Hematology · doi:10.1053/j.seminhematol.2021.06.003 · Cited by 15
Hepcidin expression in the liver of rats fed a magnesium-deficient diet
Ishizaki, N., Kotani, M., Funaba, M., & Matsui, T. (2011) · British Journal Of Nutrition · doi:10.1017/s0007114511001553 · Cited by 12
“receptor of Bmp, including Bmp6, enhances Hepcidin expression both in vitro and in vivo ((22,29,30)).”
BackgroundAraki, T., Kusakabe, M., & Nishida, E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.177907 · Cited by 12
Sex differences and steroid modulation of cardiac iron in a mouse model of iron overload
Brewer, C., Otto‐Duessel, M., Wood, R. I., & Wood, J. C. (2013) · Translational research · doi:10.1016/j.trsl.2013.08.004 · Cited by 12
IRON OVERLOAD IN SICKLE CELL DISEASE
Raghupathy, R. (2010) · Cited by 12
Lin, H.-Y., Ko, C., Lo, T.-Y., Wu, S., Lan, S.-W., Huang, C.-A., Lin, Y., Lin, H.-H., Tu, H.-F., Lee, C., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02303-z · Cited by 13
Hosoki, T., Ikuta, K., Shimonaka, Y., Sasaki, Y., Yasuno, H., Sato, K., Ohtake, T., Sasaki, K., Torimoto, Y., Saito, K., et al. (2009) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200900112 · Cited by 12
“The bone morphogenic proteins (BMPs) are members of the transforming growth factor b superfamily, and BMPs have been proposed to be involved in hemojuvelin-mediated regulation of hepcidin synthesis [12].”
BackgroundMolecular basis of hereditary iron homeostasis defects
Horváthová, M., Ponka, P., & Divoký, V. (2010) · Hematology · doi:10.1179/102453310x12583347009810 · Cited by 12
Jorge, É. C., Ahmed, M. U., Bothe, I., Coutinho, L. L., & Dietrich, S. (2012) · Developmental Dynamics · doi:10.1002/dvdy.23889 · Cited by 12
“a SPECIAL ISSUE RESEARCH ARTICLE RGMa and RGMb Expression Pattern During”
BackgroundMethodSebastiani, G., & Pantopoulos, K. (2010) · CRC Press eBooks · doi:10.1201/9781420059984-c13 · Cited by 12
Bone Morphogenetic Protein Receptors and Actions
Miyazono, K., & Shimanuki, T. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00069-0 · Cited by 12
Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function
Wu, Q., Li, S., Zhang, X., & Dong, N. (2023) · Biomedicines · doi:10.3390/biomedicines11071794 · Cited by 10
“In humans, hepcidin is encoded by the HAMP gene, which is upregulated by bone morphogenetic protein (BMP) signaling [98].”
BackgroundGurieva, I., Frýdlová, J., Rychtarčíková, Z., Vokurka, M., Truksa, J., & Krijt, J. (2017) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2017.02.007 · Cited by 11
Kaushik, S. R., Sahu, S., Guha, H., Saha, S. T., Das, R., Kupa, R.-U., Kapfo, W., Deka, T., Basumatary, R., Thong, A., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.985538 · Cited by 10
“Inflammation reduces hepatic hemojuvelin production and impacts iron sensing, whichmight behappening in theseTBpatients (Figure7B) (35, 36).”
BackgroundHuang, X., Fung, E. T., Yip, C., & Zeleniuch‐Jacquotte, A. (2008) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2008.06.009 · Cited by 11
“Bone morphogenetic proteins have been found to use hemojuvelin as a coreceptor to regulate preprohepcidin expression and to be more potent than IL-6 in stimulating preprohepcidin transcription [30,31].”
BackgroundDogan, D. Y., Urzica, E. I., Hornung, I., Kastl, P., Oguama, D., Fette, F., Nguyen, L. H., Rosenbauer, F., Zacharowski, K. D., Klingmüller, U., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023012322 · Cited by 10
Molecular diagnosis of genetic iron-overload disorders
Brissot, P., Bardou‐Jacquet, E., Troadec, M., Mosser, A., Island, M., Détivaud, L., Loréal, O., & Jouanolle, A. (2010) · Expert Review of Molecular Diagnostics · doi:10.1586/erm.10.55 · Cited by 10
Iron-regulatory gene expression during liver regeneration
Mollbrink, A., Holmström, P., Sjöström, M., Hultcrantz, R. W., Eriksson, L. C., & Stal, P. I. (2012) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2012.661761 · Cited by 9
“BMPs regulate hepcidin transcription via inducing Sma- and Mad-related protein 4 (SMAD4), which in turn regulate Smad1, Smad5, and Smad8 set of Smad proteins [7].”
BackgroundAsperti, M., Brilli, E., Denardo, A., Gryzik, M., Pagani, F., Busti, F., Tarantino, G., Arosio, P., Girelli, D., & Poli, M. (2021) · American Journal of Hematology · doi:10.1002/ajh.26311 · Cited by 10
Role of Iron Metabolism-Related Genes in Prenatal Development: Insights from Mouse Transgenic Models
Kopeć, Z., Starzyński, R. R., Jończy, A., Mazgaj, R., & Lipiński, P. (2021) · Genes · doi:10.3390/genes12091382 · Cited by 10
“Matriptase-2 (encoded by the Tmprss6 gene) is a repressor of hepcidin expression operating through the proteolytic degradation of membrane hemojuvelin [75,76], which in turn acts as a co-receptor and is required to fully activate transcription of the Hamp gene through the BMP/SMAD (bone morphogenetic protein/sons of m…”
BackgroundKoppe, T., Patchen, B., Cheng, A., Bhasin, M., Vulpe, C. D., Schwartz, R. E., Moreno‐Navarrete, J. M., Fernández‐Real, J. M., Pissios, P., & Fraenkel, P. G. (2017) · Hepatology Communications · doi:10.1002/hep4.1083 · Cited by 10
“Deficiency in hepcidin or HJV is associated with iron overload both in human patients and in mouse models.((6-9)) As the prevalence of obesity is rising throughout the developed world and is associated with increased rates of diabetes, hyperlipidemia, and steatohepatitis, the interplay of energy metabolism and iron me…”
BackgroundSeiki, T., Naito, M., Hishida, A., Takagi, S., Matsunaga, T., Sasakabe, T., Hattori, Y., Kawai, S., Okada, R., Yin, G., et al. (2017) · Gene · doi:10.1016/j.gene.2017.11.031 · Cited by 8
A severe hemojuvelin mutation leading to late onset of HFE2 -hemochromatosis
Ravasi, G., Pelucchi, S., Mariani, R., Silvestri, L., Camaschella, C., & Piperno, A. (2018) · Digestive and Liver Disease · doi:10.1016/j.dld.2018.04.018 · Cited by 10
Effect of tetramethylpyrazine and hyperlipidemia on hepcidin homeostasis in mice
Zhang, M., Sun, M., Guo, C., Wang, J., Xu, F., & Yin, H.-J. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3968 · Cited by 10
Sun, Z., Cai, S., Zabkiewicz, C., Liu, C., & Ye, L. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.5030 · Cited by 10
“In addition to these negative regulators, there are positive regulators for the BMP pathway, such as co-receptors, which enhance BMP signalling (25,42-44).”
BackgroundHuang, H., Zuzarte‐Luís, V., Fragoso, G., Calvé, A., Hoang, T. A., Oliero, M., Chabot‐Roy, G., Mullins‐Dansereau, V., Lesage, S., & Santos, M. M. (2020) · Scientific Reports · doi:10.1038/s41598-020-78037-3 · Cited by 10
Dimitriadis, A., Foka, P., Kyratzopoulou, E., Karamichali, E., Petroulia, S., Tsitoura, P., Kakkanas, A., Eliadis, P., Georgopoulou, U., & Mamalaki, A. (2020) · FEBS Open Bio · doi:10.1002/2211-5463.13048 · Cited by 10
Copola, A. G. L., dos Santos, Í. G. D., Coutinho, L. L., Del‐Bem, L., Campos-Júnior, P. H. A., Mamede, I., Nogueira, J. M., Costa, A. C., Silva, G. A. B., & Jorge, É. C. (2022) · BMC Genomics · doi:10.1186/s12864-022-08396-w · Cited by 9
Srai, S. K., & Sharp, P. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_1 · Cited by 11
Acidic milieu augments the expression of hepcidin, the central regulator of iron homeostasis
Mizumoto, C., Kawabata, H., Uchiyama, T., Sakamoto, S., Kanda, J., Tomosugi, N., & Takaori‐Kondo, A. (2012) · International Journal of Hematology · doi:10.1007/s12185-012-1223-6 · Cited by 10
“Previous studies have shown that HJV is a co-receptor of BMP receptors, and BMP6 stimulates the hepcidin promoter via the SMAD pathway [9, 27–29].”
BackgroundHomocysteine upregulates hepcidin expression through BMP6/SMAD signaling pathway in hepatocytes
Luo, X., Luo, Z., Zhang, Z., Yang, H., Lai, B., Yao, Q., Xiao, L., & Wang, N. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.02.001 · Cited by 10
Wang, K., Hou, M., Qiao, C., Duan, Y., Tao, R., Wang, X., Xiao, K., Liu, S., Zhao, H., Wang, J., et al. (2024) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2024.02.013 · Cited by 9
Role of Ferroptosis in ALD: Focusing on Hepcidin and Besides Hepcidin
Chen, L., Zhou, H., Cheng, Z., Liu, D., & Tan, Y. (2024) · Current Medicinal Chemistry · doi:10.2174/0109298673317526240924050651 · Cited by 9
Exposure to Endotoxin Oxidized by Atmospheric Ozone Greatly Enhances Anemia
Liu, H., Xing, Q., Zhu, C., Wang, Q., Lu, K., Guo, S., Wu, Z., Hu, M., Li, S., & Yao, M. (2025) · Environmental Science & Technology · doi:10.1021/acs.est.4c14589 · Cited by 9
Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies in Mask Mice
Krijt, J., Frýdlová, J., Gurieva, I., Přikryl, P., Báječný, M., Steinbicker, A. U., Vokurka, M., & Truksa, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052650 · Cited by 9
“The most important signaling pathway which regulates the expression of hepcidin in response to iron availability is the BMP-SMAD signaling pathway [8,31].”
BackgroundSkrypnik, K., Olejnik‐Schmidt, A., Mikołajczyk-Stecyna, J., SCHMIDT, M. T., & Suliburska, J. (2022) · Journal of Functional Foods · doi:10.1016/j.jff.2022.105205 · Cited by 9
WU, J., Liao, Q., ZHANG, L., WU, S., & LIU, Z. (2023) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.32604/or.2023.031404 · Cited by 10
“In addition, the bone morphogenetic protein (BMP) family and other members of the TGF family transcriptionally control HAMP expression [53].”
BackgroundAn Update on Iron Homeostasis: Make New Friends, but Keep the Old
Roy, C. N. (2013) · The American Journal of the Medical Sciences · doi:10.1097/maj.0000000000000190 · Cited by 9
“The identification of repulsive guidance molecule family members as coreceptors, which enhance signaling of the bone morphogenetic protein (Bmp) family, led to the discovery that Hjv is a Bmp coreceptor(63) that signals through the Smad (mammalian homolog of Caenorhabditis elegans “small body size” and Drosophila “mot…”
BackgroundDesign and Rationale for the Study of Changes in Iron and Atherosclerosis Risk in Perimenopause
Mihai, G., He, X., Zhang, X., Carthy, B. M., & Tran, T. (2011) · Journal of Clinical & Experimental Cardiology · doi:10.4172/2155-9880.1000152 · Cited by 8
Liver and serum iron: Discrete regulators of hepatic hepcidin expression
Chua, A. C. G., Trinder, D., & Olynyk, J. K. (2011) · Hepatology · doi:10.1002/hep.24449 · Cited by 9
“HJV has been shown to interact directly with BMP6,(2) and their interaction facilitates activation of the BMPR complex and enhances BMP-SMAD signaling to modulate hepcidin expression.(3) Although several BMPs including BMP2, 4, 5, 6, 7, and 9 can stimulate hepcidin expression,(3-5) BMP6 is physiologically the most rel…”
BackgroundNikkari, S. T., Visto, A.-L., Määttä, K. M., & Kunnas, T. A. (2017) · Medicine · doi:10.1097/md.0000000000006052 · Cited by 9
Deficiency of the BMP Type I receptor ALK3 partly protects mice from anemia of inflammation
Gallitz, I., Lofruthe, N., Traeger, L., Bäumer, N., Hoerr, V., Faber, C., Kuhlmann, T., Müller‐Tidow, C., & Steinbicker, A. U. (2018) · BMC Physiology · doi:10.1186/s12899-018-0037-z · Cited by 9
“In addition, transcriptional regulation of hepcidin requires BMP signalling [8].”
BackgroundPolycythemia in Patients With Hereditary Hemochromatosis: Real or Myth?
Asif, S., Begemann, M. E., & Raza, S. (2019) · Journal of Clinical Medicine Research · doi:10.14740/jocmr3816 · Cited by 9
“Hepcidin synthesis is controlled by plasma iron levels and body iron stores in a negative feedback manner which involves regulatory ligands such as hemojuvelin (HJV), transferrin receptors 1 and 2 and HFE transmembrane protein [16, 17].”
Background[Progress on epigenetic regulation of iron homeostasis].
Duan, L., Yin, X., Meng, H., Fang, X., Min, J., & Wang, F. (2020) · PubMed · doi:10.3785/j.issn.1008-9292.2020.02.25 · Cited by 9
Martins, A. F., Neto, J. X., Azambujá, A. P., Sereno, M. L., Figueira, A., Campos-Júnior, P. H. A., do Rosário, M. F., Toledo, C. B. B., Silva, G. A. B., Kitten, G. T., et al. (2014) · Cells Tissues Organs · doi:10.1159/000433491 · Cited by 8
“RGMc was described as the skeletal muscle member of this family, which was involved in the regulation of hepcidin expression [Babitt et al., 2005, 2006; Truksa et al., 2006] and of iron homeostasis [reviewed by Papanikolaou et al., 2003].”
BackgroundCrosstalk between Erythropoiesis and Iron Metabolism
Rivella, S., Nemeth, E., & Miller, J. L. (2010) · Advances in Hematology · doi:10.1155/2010/317095 · Cited by 9
“HFE associates with TfR1 under low iron conditions [85] and is displaced when TfR1 binds TfFe(III) [86–88] (Figure 2).”
BackgroundAnemia de las enfermedades crónicas asociada a obesidad: papel de la hepcidina como mediador central
Pía Villarroel, H., Arredondo, M., & Manuel Olivares, G. (2013) · Revista médica de Chile · doi:10.4067/s0034-98872013000700008 · Cited by 9
Deregulation of Hepatic Mek1/2–Erk1/2 Signaling Module in Iron Overload Conditions
Tangudu, N. K., Buth, N., Strnad, P., Cirstea, I. C., & Spasić, M. V. (2019) · Pharmaceuticals · doi:10.3390/ph12020070 · Cited by 9
Macrophages and Iron Metabolism
Ganz, T. (2017) · ASM Press eBooks · doi:10.1128/9781555819194.ch46 · Cited by 10
Novel observations in hereditary hemochromatosis: potential implications for clinical strategies
Swinkels, D. W., & Fleming, R. E. (2011) · Haematologica · doi:10.3324/haematol.2011.042036 · Cited by 9
“Hemojuvelin is a BMP-coreceptor which augments the BMP signal.(6) Circulating transferrin appears to be sensed via a hepatocellular complex which includes TFR1, TFR2 and HFE.”
RGM Family Involved in the Regulation of Hepcidin Expression in Anemia of Chronic Disease
Fujii, T., Kobayashi, K., Kaneko, M., Osana, S., Tsai, C.-T., Ito, S., & Hata, K. (2024) · Immuno · doi:10.3390/immuno4030017 · Cited by 11
Iron, the Essential Micronutrient: A Comprehensive Review of Regulatory Pathways of Iron Metabolism
Horváth, A., Tamási, K., Pap, R., Jánosa, G., & Pandur, E. (2025) · Nutrients · doi:10.3390/nu18010109 · Cited by 12
“These interactions between the three membrane proteins participate in the transmission of increased Tf-Fe levels and the activation of hepcidin transcription [64–66].”
Nili, M., David, L. L., Elferich, J., Shinde, U. P., & Rotwein, P. S. (2013) · Biochemical Journal · doi:10.1042/bj20121845 · Cited by 8
“Haemochromatotic” characteristics of the human BEL ‐7402 cell line
Xu, A., Li, Y., Chen, W., Li, X., Zhang, W., Li, S., Wu, L., Wu, Z., Zhang, B., Ou, X., et al. (2017) · British Journal of Haematology · doi:10.1111/bjh.14952 · Cited by 8
Juvenile Hereditary Hemochromatosis
Goldberg, Y. P. (2011) · Cited by 8
Gnana‐Prakasam, J. P., Baldowski, R. B., Ananth, S., Martin, P. M., Smith, S. B., & Ganapathy, V. (2014) · Europe PMC (PubMed Central) · Cited by 8
Allameh, A., Hüttmann, N., Charlebois, E., Katsarou, A., Gu, W., Gkouvatsos, K., Pasini, E., Bhat, M., Minić, Z., Berezovski, M. V., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03108-2 · Cited by 9
Iron Metabolism and Related Disorders
Hoda, K., Bowlus, C. L., Chu, T. W., & Gruen, J. R. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00106-3 · Cited by 8
Iron Metabolism in Humans: An Overview
Arora, S., & Kapoor, R. (2012) · BiblioBoard Library Catalog (Open Research Library) · doi:10.5772/39031 · Cited by 8
“This membrane-bound hemojuvelin (m-HJV) is capable of binding BMPs, facilitating their association with the BMP receptor [64].”
Ka, C., Gac, G. L., Létocart, É., Gourlaouen, I., Martin, B., & Férec, C. (2007) · Haematologica · doi:10.3324/haematol.11247 · Cited by 8
“an important mechanism for regulating hepcidin expression.(6) To demonstrate causality of p.”
BackgroundDiagnosis and Management of Iron Deficiency Anaemia in Children — A Clinical Update
Chew, C. S. E., & Lam, J. C. M. (2012) · Proceedings of Singapore Healthcare · doi:10.1177/201010581202100410 · Cited by 8
Paterson, A. C., & Pietrangelo, A. (2011) · Elsevier eBooks · doi:10.1016/b978-0-7020-3398-8.00005-2 · Cited by 9
Frýdlová, J., Rogalsky, D. W., Truksa, J., Nečas, E., Vokurka, M., & Krijt, J. (2019) · PLoS ONE · doi:10.1371/journal.pone.0215028 · Cited by 7
Regulation of Iron Absorption and Distribution
Latunde-Dada, G. O., & Simpson, R. J. (2009) · Humana Press eBooks · doi:10.1007/978-1-59745-462-9_2 · Cited by 8
“the BMP/Smad, STAT3 and ERK/p38MAP kinase signal transduction pathways are involved in the transcriptional regulation of hepcidin expression (Babitt et al., 2006; Calzolari et al., 2006; Verga Falzacappa et al., 2007; Wrighting & Andrews, 2006).”
BackgroundAnemia in End Stage Renal Disease
Jalalzadeh, M. (2021) · Nephro-Urology Monthly · doi:10.5812/numonthly.109246 · Cited by 8
Cross-talk between iron homeostasis and intestinal inflammation
Cherayil, B. J. (2010) · Gut Microbes · doi:10.4161/gmic.1.1.10863 · Cited by 8
Hepcidin Regulation by Bone Morphogenetic Protein Signaling and Iron Homeostasis
Rodova, M., & Kim, S. (2016) · Journal of Nutrition & Food Sciences · doi:10.4172/2155-9600.1000521 · Cited by 7
“Mutations in HJV cause decreased BMP signaling, resulting in decreased hepcidin expression, followed by severe iron overload [33] and HH.”
BackgroundUnveiling the Impact of BMP9 in Liver Diseases: Insights into Pathogenesis and Therapeutic Potential
Chen, H., Li, Y.-Y., Nio, K., & Tang, H. (2024) · Biomolecules · doi:10.3390/biom14081013 · Cited by 8
“BMP ligands can regulate the hepcidin levels through BMP receptors and the co-receptor hemojuvelin with the exception of BMP9, which does not interact functionally with hemojuvelin [147].”
BackgroundRetinoids as Promising Treatment for Non-alcoholic Fatty Liver Disease
Tsuchiya, H. (2012) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.132.903 · Cited by 7
Panda, S., Faisal, S., Kumar, K. S., Seelan, D. M., Sharma, A., Gupta, N. K., Datta, S. K., & Singh, A. (2021) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-020-00947-w · Cited by 7
Hegde, N. V., Unger, E. L., Jensen, G. L., Hankey, P. A., & Paulson, R. F. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00463.2010 · Cited by 7
“Variation in hepcidin expression by transcriptional regulators primarily acts through IL-6/STAT3 and BMP/Smad signaling pathways (4).”
BackgroundTransferrin receptor 2 is emerging as a major player in the control of iron metabolism
Calzolari, A., Oliviero, I., & Testa, U. (2007) · Open Life Sciences · doi:10.2478/s11535-007-0007-0 · Cited by 7
Zhang, H., Shi, H., Zhou, S., Meng, M., Ma, N., Chang, G., & Shen, X. (2025) · Journal of Dairy Science · doi:10.3168/jds.2024-25557 · Cited by 6
Mendelian randomization analysis to identify potential drug targets for osteoarthritis
Lu, C., Xu, Y., Chen, S., Guo, L., Li, P., Wei, X., & Rong, X. (2025) · PLoS ONE · doi:10.1371/journal.pone.0316824 · Cited by 6
Amamoto, S., Yoshiga, D., Tabe, S., Kokabu, S., Fujii, W., Hikiji, H., Tominaga, K., & Yoshioka, I. (2022) · Journal of Oral and Maxillofacial Surgery Medicine and Pathology · doi:10.1016/j.ajoms.2022.01.007 · Cited by 6
Wang, C., Melgar-Bermudez, E., Welch, D., Dagbay, K. B., Bhattacharya, S., Lema, E., Daman, T. H., Sierra, O., Todorova, R., Drame, P. M., et al. (2025) · American Journal of Hematology · doi:10.1002/ajh.27578 · Cited by 7
Repulsive guidance molecule acts in axon branching in Caenorhabditis elegans
Tsutsui, K., Kim, H., Yoshikata, C., Kimura, K., Kubota, Y., Shibata, Y., Tian, C., Liu, J., & Nishiwaki, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-01853-8 · Cited by 6
Host-Directed Therapies for Tuberculosis
Venketaraman, V. (2020) · MDPI eBooks · doi:10.3390/books978-3-03943-502-9 · Cited by 6
New Players in Neuronal Iron Homeostasis: Insights from CRISPRi Studies
Bórquez, D. A., Castro, F. B. D., Núñez, M. T., & Urrutia, P. J. (2022) · Antioxidants · doi:10.3390/antiox11091807 · Cited by 6
“This phenotype is attributed to a hepatic deficiency of hemojuvelin (HJV), a GPI-anchored protein [56] that regulates the transcription of hepcidin, a cytokine that acts as the master regulator of systemic iron homeostasis [57].”
BackgroundSkrypnik, K., Olejnik‐Schmidt, A., Mikołajczyk-Stecyna, J., SCHMIDT, M. T., & Suliburska, J. (2024) · Nutrition · doi:10.1016/j.nut.2024.112591 · Cited by 6
Repulsive Guidance Molecule b (RGMb) Is Dispensable for Normal Gonadal Function in Mice1
Meng, C., Liu, W., Huang, H., Wang, Y., Chen, B., Freeman, G. J., Schneyer, A. L., Lin, H. Y.-F., & Xia, Y. Y. (2016) · Biology of Reproduction · doi:10.1095/biolreprod.115.135921 · Cited by 6
Shi, Y., & Pan, X. (2016) · Genetics and Molecular Research · doi:10.4238/gmr.15017130 · Cited by 6
“This suggests that BMP6 expression may be closely associated with the occurrence of CRA, which is consistent with previously published studies (Babitt et al., 2006; Andriopoulos Jr. et al., 2009).”
ResultInfluentialIron and aluminum in Alzheimer's disease.
Lorenzo, F. D., & Lorenzo, B. D. (2013) · PubMed · Cited by 6
Hino, K., & Harada, M. (2016) · Springer eBooks · doi:10.1007/978-4-431-55790-6_7 · Cited by 6
Basic Understanding of Iron Metabolism
Suh, J. K., & Jeon, I. S. (2018) · Imsang soa hyeoraek jong-yang/Imsang soa hyeol'aeg jong'yang/Clinical pediatric hematology-oncology · doi:10.15264/cpho.2018.25.1.1 · Cited by 6
“BMP가 hepcidin 유전자의 촉진자(promoter)에 결합하여 hepcidin의 합성을 촉진시킬 수 있도록 한다[27,29].”
Valenzuela‐Muñoz, V., Benavente, B. P., Casuso, A., Leal, Y., Valenzuela‐Miranda, D., Núñez-Acuña, G., Sáez-Vera, C., & Gallardo‐Escárate, C. (2021) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2021.08.005 · Cited by 6
Asimakopoulou, A., Weiskirchen, S., & Weiskirchen, R. (2017) · European Medical Journal · doi:10.33590/emj/10310080 · Cited by 7
Torti, S. V., Lemler, E., & Mueller, B. K. (2016) · Clinical and Experimental Pharmacology · doi:10.4172/2161-1459.1000223 · Cited by 5
“For example, BMPs induce hepcidin synthesis in breast, prostate and liver cancer cells [7-19].”
Hepatocyte-specific deletion of peroxisomal protein PEX13 results in disrupted iron homeostasis
Rishi, G., Bhatia, M., Secondes, E. S., Melino, M., Crane, D. I., & Subramaniam, V. N. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165882 · Cited by 6
Kim, Y., Park, W., Choi, B., Choi, H., & Kim, D. (2021) · Antioxidants · doi:10.3390/antiox10101590 · Cited by 6
“Briefly, HepG2 cells were transfected with FLAG-SMILE, HA-SMAD1, HA-SMAD5, HA-SMAD8 and HASMAD4 for 48 h. Whole-cell lysates (200 µL) were immunoprecipitated with anti-FLAG M2 affinity gel and eluted with 3× FLAG peptide.”
BackgroundInfluentialPhysiopathologie et génétique de l'hémochromatose HFE de type 1
Loréal, O., Ropert, M., Mosser, A., Déhais, V., Deugnier, Y., David, V., Brissot, P., & Jouanolle, A. (2007) · La Presse Médicale · doi:10.1016/j.lpm.2007.03.038 · Cited by 7
Novel tools for the evaluation of iron metabolism
Kautz, L., & Nemeth, E. (2010) · Haematologica · doi:10.3324/haematol.2010.033993 · Cited by 6
“Like other members of this family, it is a co-receptor for bone morphogenetic proteins (BMP) and potentiates BMP pathway signaling.(4) The BMP signaling cascade is initiated by BMP binding to a complex composed of two type I and two type II BMP receptors, and hemojuvelin appears to increase the utilization of specific…”
BackgroundXiao, X., Moschetta, G. A., Chowdhury, S. B., Phillips, S., Ghatpande, N., Fisher, A. L., Xue, Y., & Babitt, J. L. (2025) · American Journal of Hematology · doi:10.1002/ajh.70055 · Cited by 5
Liu, J., Qian, L., Guo, L., & Feng, Y.-Z. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7876 · Cited by 5
“The most two important signaling pathways for hepcidin expression are the bone morphogenetic protein 6 (BMP6) (13) and Janus kinase2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal pathways (14).”
Metadata
- Authors
- 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., Andrews, N. C., & Lin, H. Y.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lin, Herbert Y
- ORCID
- Venue
- Nature Genetics
- Published
- 2006-04-09
- Volume
- 38
- Issue
- 5
- Pages
- 531-539
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2050833520
- Cited by
- 1,026
- References
- 52
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 21 · 2023: 22 · 2022: 21 · 2021: 54 · 2020: 35 · 2019: 39 · 2018: 39 · 2017: 50 · 2016: 44 · 2015: 50 · 2014: 58 · 2013: 62 · 2012: 67
- FWCI
- 49.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL07623, T32HL007623)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-71837, R01DK066373, DK-69533, K08DK075846, R01DK071837, F32DK068997, R01DK069533)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- hemojuvelin, hepcidin, BMP signaling, iron homeostasis, hemochromatosis, RGMa, dragons, hepatocytes, iron overload, anemia
- MeSH terms
- Hemochromatosis Protein, Amino Acid Sequence, Animals, Gene Expression Regulation, Cricetinae, Humans, Liver, Membrane Proteins, Molecular Sequence Data, Mutation, Signal Transduction, Polymerase Chain Reaction, Transforming Growth Factor beta, CHO Cells, Bone Morphogenetic Proteins, Antimicrobial Cationic Peptides, Bone Morphogenetic Protein 2, GPI-Linked Proteins, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
