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Hemojuvelin

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https://www.readbyqxmd.com/read/29404495/nicotinamide-n-methyltransferase-expression-decreases-in-iron-overload-exacerbating-toxicity-in-mouse-hepatocytes
#1
Tiago Koppe, Bonnie Patchen, Aaron Cheng, Manoj Bhasin, Chris Vulpe, Robert E Schwartz, Jose Maria Moreno-Navarrete, Jose Manuel Fernandez-Real, Pavlos Pissios, Paula G Fraenkel
Iron overload causes the generation of reactive oxygen species that can lead to lasting damage to the liver and other organs. The goal of this study was to identify genes that modify the toxicity of iron overload. We studied the effect of iron overload on the hepatic transcriptional and metabolomic profile in mouse models using a dietary model of iron overload and a genetic model, the hemojuvelin knockout mouse. We then evaluated the correlation of nicotinamide N-methyltransferase (NNMT) expression with body iron stores in human patients and the effect of NNMT knockdown on gene expression and viability in primary mouse hepatocytes...
October 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29390526/genetic-variation-in-bone-morphogenetic-proteins-family-members-bmps-2-and-4-and-hypertension-risk-in-middle-aged-men-the-tamrisk-study
#2
Jaakko V I Piesanen, Seppo T Nikkari, Tarja A Kunnas
Bone morphogenetic proteins (BMPs) are important regulators of iron metabolism affecting hepcidin expression. We have previously shown that 2 genetic polymorphisms in different genes (histocompatibility complex class I-like transmembrane protein, hemojuvelin) involved in the regulation of hepcidin expression pathways are associated with hypertension. In this study, we analyzed genetic variation sites in BMP2 (rs235756, rs235768) and BMP4 (rs4901474) to get more evidence linking iron metabolism to hypertension risk in the Finnish population...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29386545/hemojuvelin-predicts-acute-kidney-injury-and-poor-outcomes-following-cardiac-surgery
#3
Sheng-Wen Ko, Nai-Hsin Chi, Che-Hsiung Wu, Tao-Min Huang, Shih-Chieh Jeff Chueh, Chih-Hsien Wang, Jui-Hsiang Lin, Wei-Jie Wang, Jui-Tsung Ting, Huang-Ming Chang, Rory Connolly, Chien-Heng Lai, Li-Jung Tseng, Vin-Cent Wu, Tzong-Shinn Chu
Acute kidney injury (AKI) is detrimental after cardiac surgery. In this multicenter study, the novel biomarker hemojuvelin (HJV) was evaluated for AKI prediction following cardiac surgery. Urinary HJV, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine were measured in 151 patients after surgery. The outcomes of advanced AKI (KDIGO stages 2 and 3) and all causes of in-hospital mortality as the composite outcome were recorded. Areas under the receiver operator characteristic curves (AUC) and a multivariate generalized additive model (GAM) were applied to predict these outcomes of interest...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29208771/advanced-iron-overload-cardiomyopathy-in-a-genetic-murine-model-is-rescued-by-resveratrol-therapy
#4
Subhash K Das, Pavel Zhabyeyev, Ratnadeep Basu, Vaibhav B Patel, Jason R B Dyck, Zamaneh Kassiri, Gavin Y Oudit
Iron-overload cardiomyopathy is prevalent on a worldwide basis and is a major comorbidity in patients with genetic hemochromatosis and secondary iron overload. Therapies are limited in part due to lack of a valid preclinical model, which recapitulates advanced iron-overload cardiomyopathy. Male hemojuvelin (HJV) knockout (HJVKO) mice, which lack HJV, a bone morphogenetic co-receptor protein required for hepcidin expression and systemic iron homeostasis, were fed a high-iron diet starting at 4 weeks of age for a duration of 1 year...
February 28, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29134618/the-mechanisms-of-systemic-iron-homeostasis-and-etiology-diagnosis-and-treatment-of-hereditary-hemochromatosis
#5
REVIEW
Hiroshi Kawabata
Hereditary hemochromatosis (HH) is a group of genetic iron overload disorders that manifest with various symptoms, including hepatic dysfunction, diabetes, and cardiomyopathy. Classic HH type 1, which is common in Caucasians, is caused by bi-allelic mutations of HFE. Severe types of HH are caused by either bi-allelic mutations of HFE2 that encodes hemojuvelin (type 2A) or HAMP that encodes hepcidin (type 2B). HH type 3, which is of intermediate severity, is caused by bi-allelic mutations of TFR2 that encodes transferrin receptor 2...
January 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29073189/effect-of-erythropoietin-administration-on-proteins-participating-in-iron-homeostasis-in-tmprss6-mutated-mask-mice
#6
Jana Frýdlová, Zuzana Rychtarčíková, Iuliia Gurieva, Martin Vokurka, Jaroslav Truksa, Jan Krijt
Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice...
2017: PloS One
https://www.readbyqxmd.com/read/29021231/deletion-of-bmp6-worsens-the-phenotype-of-hjv-deficient-mice-and-attenuates-hepcidin-levels-reached-after-lps-challenge
#7
Chloé Latour, Céline Besson-Fournier, Ophélie Gourbeyre, Delphine Meynard, Marie-Paule Roth, Hélène Coppin
Lack of either bone morphogenetic protein 6 (BMP6) or the BMP coreceptor hemojuvelin (HJV) in mice leads to a similar phenotype with hepcidin insufficiency, hepatic iron loading, and extrahepatic iron accumulation in males. This is consistent with the current views that HJV is a coreceptor for BMP6 in hepatocytes. To determine whether BMP6 and HJV may also signal to hepcidin independently of each other, we intercrossed Hjv -/- and Bmp6 -/- mice and compared the phenotype of animals of the F2 progeny. Loss of Bmp6 further repressed Smad signaling and hepcidin expression in the liver of Hjv -/- mice of both sexes, and led to iron accumulation in the pancreas and the heart of females...
November 23, 2017: Blood
https://www.readbyqxmd.com/read/28978826/progress-in-iron-metabolism-research
#8
Hiroshi Kawabata
Iron is essential for various cellular processes, but an excess of iron may cause organ damage through the production of reactive oxygen species. Therefore, the amount of iron in the body must be strictly controlled. The central regulator of systemic iron homeostasis is hepcidin, which is primarily produced in the liver. Various molecules, including HFE, transferrin receptor 2 (TFR2), and hemojuvelin (HJV), are involved in sensing systemic iron status. Hepatocytes produce hepcidin in response to excess iron and inflammatory stimuli (e...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28935635/serpinb3-is-overexpressed-in-the-liver-in-presence-of-iron-overload
#9
Cristian Turato, Patricia Kent, Giada Sebastiani, Stefania Cannito, Elisabetta Morello, Liliana Terrin, Alessandra Biasiolo, Davide Simonato, Maurizio Parola, Kostas Pantopoulos, Patrizia Pontisso
Iron overload results in cellular toxicity, tissue injury, organ fibrosis and increased risk of neoplastic transformation. SerpinB3 is a serine protease inhibitor overexpressed in the liver in oxidative stress conditions, able to induce fibrosis and increased risk of malignant transformation. Aim of the present study was to assess the effect of iron overload on SerpinB3 expression in the liver using in vivo and in vitro models.The expression of Serpinb3 was assessed in the liver of hemojuvelin knockout mice (Hjv-/-), an established model of hereditary hemochromatosis, and of wild type control mice, following dietary or pharmacological iron manipulation...
January 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28924039/matriptase-2-suppresses-hepcidin-expression-by-cleaving-multiple-components-of-the-hepcidin-induction-pathway
#10
Mastura Wahedi, Aaron M Wortham, Mark D Kleven, Ningning Zhao, Shall Jue, Caroline A Enns, An-Sheng Zhang
Systemic iron homeostasis is maintained by regulation of iron absorption in the duodenum, iron recycling from erythrocytes, and iron mobilization from the liver and is controlled by the hepatic hormone hepcidin. Hepcidin expression is induced via the bone morphogenetic protein (BMP) signaling pathway that preferentially uses two type I (ALK2 and ALK3) and two type II (ActRIIA and BMPR2) BMP receptors. Hemojuvelin (HJV), HFE, and transferrin receptor-2 (TfR2) facilitate this process presumably by forming a plasma membrane complex with BMP receptors...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28815688/bone-morphogenetic-protein-2-controls-iron-homeostasis-in-mice-independent-of-bmp6
#11
Susanna Canali, Chia-Yu Wang, Kimberly B Zumbrennen-Bullough, Abraham Bayer, Jodie L Babitt
Hepcidin is a key iron regulatory hormone that controls expression of the iron exporter ferroportin to increase the iron supply when needed to support erythropoiesis and other essential functions, but to prevent the toxicity of iron excess. The bone morphogenetic protein (BMP)-SMAD signaling pathway, through the ligand BMP6 and the co-receptor hemojuvelin, is a central regulator of hepcidin transcription in the liver in response to iron. Here, we show that dietary iron loading has a residual ability to induce Smad signaling and hepcidin expression in Bmp6-/- mice, effects that are blocked by a neutralizing BMP2/4 antibody...
November 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28815056/hemojuvelin-regulates-the-innate-immune-response-to-peritoneal-bacterial-infection-in-mice
#12
Qian Wu, Yuanyuan Shen, Yunlong Tao, Jiayu Wei, Hao Wang, Peng An, Zhuzhen Zhang, Hong Gao, Tianhua Zhou, Fudi Wang, Junxia Min
Hereditary hemochromatosis and iron imbalance are associated with susceptibility to bacterial infection; however, the underlying mechanisms are poorly understood. Here, we performed in vivo bacterial infection screening using several mouse models of hemochromatosis, including Hfe (Hfe(-/-) ), hemojuvelin (Hjv(-/-) ), and macrophage-specific ferroportin-1 (Fpn1(fl/fl) ;LysM-Cre(+) ) knockout mice. We found that Hjv(-/-) mice, but not Hfe(-/-) or Fpn1(fl/fl) ;LysM-Cre(+) mice, are highly susceptible to peritoneal infection by both Gram-negative and Gram-positive bacteria...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28219045/modulating-the-selectivity-of-matriptase-2-inhibitors-with-unnatural-amino-acids
#13
Catherine St-Georges, Antoine Désilets, François Béliveau, Mariana Ghinet, Sébastien P Dion, Éloic Colombo, Pierre-Luc Boudreault, Rafael J Najmanovich, Richard Leduc, Éric Marsault
Matriptase-2, a type II transmembrane serine protease (TTSP), is expressed in the liver and regulates iron homeostasis via the cleavage of hemojuvelin. Matriptase-2 emerges as an attractive target for the treatment of conditions associated with iron overload, such as hemochromatosis or beta-thalassemia. Starting from the crystal structure of its closest homolog matriptase, we constructed a homology model of matriptase-2 in order to further optimize the selectivity of serine trap peptidomimetic inhibitors for matriptase-2 vs matriptase...
March 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28203489/effects-of-anti-repulsive-guidance-molecule-c-rgmc-hemojuvelin-antibody-on-hepcidin-and-iron-in-mouse-liver-and-tumor-xenografts
#14
S V Torti, E Lemler, B K Mueller, A Popp, F M Torti
OBJECTIVE: Hepcidin is a peptide hormone produced by the liver that regulates systemic iron homeostasis. Hepcidin is also synthesized by tumors, where it contributes to tumor growth by increasing the tumoral retention of iron. Targeted reduction of hepcidin may therefore be useful in reducing tumor growth. H5F9-AM8 is an antibody in preclinical development for the anemia of chronic disease that reduces hepcidin synthesis by binding to RGMc, a co-receptor involved in the transcriptional induction of hepcidin by BMP6...
November 2016: Clinical & Experimental Pharmacology
https://www.readbyqxmd.com/read/28151915/minor-variant-of-rs-16827043-in-the-iron-regulator-hemojuvelin-gene-hjv-contributes-to-hypertension-the-tamrisk-study
#15
Seppo T Nikkari, Anni-Laura Visto, Kirsi M Määttä, Tarja A Kunnas
It is known that iron overload may lead to an increased risk for many diseases. According to GWAS studies, iron regulatory protein HFE gene variant H63D (rs1799945) was associated with hypertension, an observation which we were able to confirm also in our TAMRISK cohort. Thus, it is possible that abnormalities in iron homeostasis may predispose to hypertension. This prompted us to study whether there is an association between hypertension and another iron overload-associated gene, hemojuvelin (HJV), which has 2 common polymorphic sites (rs 16827043, rs7536827)...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28130911/the-relationship-of-serum-hemojuvelin-and-hepcidin-levels-with-iron-level-and-erythropoietin-requirement-in-prevalent-hepatitis-c-virus-positive-hemodialysis-patients
#16
Heba W El Said, Khaled H Abou Seif, Yasser S Ahmed, Hesham A Abou Elleil, Tamer W El Said, Maha A Behairy, Mohamed M Mohamed, Fatma A Ahmed
BACKGROUND: Iron overload is frequently reported in hemodialysis (HD) patients particularly those with chronic hepatitis C virus (HCV) infection. Soluble Hemojuvelin (sHJV) has recently emerged as one of the significant regulators of iron homeostasis and hepcidin expression. AIMS: to evaluate the potential associations of sHJV and hepcidin with inflammation, iron parameters and Erythropoietin requirement in prevalent HD patients with HCV. METHODS: Serum sHJV and hepcidin were measured in 60 prevalent HD patients with [group I (n = 30)] and without [group II (n = 30)] HCV, and controls (n = 30) by enzyme-linked immunosorbent assay...
January 28, 2017: Nephrology
https://www.readbyqxmd.com/read/28115312/females-are-protected-from-iron-overload-cardiomyopathy-independent-of-iron-metabolism-key-role-of-oxidative-stress
#17
Subhash K Das, Vaibhav B Patel, Ratnadeep Basu, Wang Wang, Jessica DesAulniers, Zamaneh Kassiri, Gavin Y Oudit
BACKGROUND: Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. METHODS AND RESULTS: Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis...
January 23, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28007423/rgms-structural-insights-molecular-regulation-and-downstream-signaling
#18
REVIEW
Christian Siebold, Toshihide Yamashita, Philippe P Monnier, Bernhard K Mueller, R Jeroen Pasterkamp
Although originally discovered as neuronal growth cone-collapsing factors, repulsive guidance molecules (RGMs) are now known as key players in many fundamental processes, such as cell migration, differentiation, iron homeostasis, and apoptosis, during the development and homeostasis of many tissues and organs, including the nervous, skeletal, and immune systems. Furthermore, three RGMs (RGMa, RGMb/DRAGON, and RGMc/hemojuvelin) have been linked to the pathogenesis of various disorders ranging from multiple sclerosis (MS) to cancer and juvenile hemochromatosis (JHH)...
May 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/27896572/identification-of-novel-mutations-in-hfe-hfe2-tfr2-and-slc40a1-genes-in-chinese-patients-affected-by-hereditary-hemochromatosis
#19
Yongwei Wang, Yali Du, Gang Liu, Shanshan Guo, Bo Hou, Xianyong Jiang, Bing Han, Yanzhong Chang, Guangjun Nie
Hereditary hemochromatosis (HH) is a group of inherited iron-overload disorders associated with pathogenic defects in the genes encoding hemochromatosis (HFE), hemojuvelin (HJV/HFE2), hepcidin (HAMP), transferrin receptor 2 (TfR2), and ferroportin (FPN1/SLC40A1) proteins, and the clinical features are well described. However, there have been only a few detailed reports of HH in Chinese populations. Thus, there is insufficient patient information for population-based analyses in Chinese populations or comparative studies among different ethical groups...
April 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27864295/endothelial-cells-produce-bone-morphogenetic-protein-6-required-for-iron-homeostasis-in-mice
#20
Susanna Canali, Kimberly B Zumbrennen-Bullough, Amanda B Core, Chia-Yu Wang, Manfred Nairz, Richard Bouley, Filip K Swirski, Jodie L Babitt
Bone morphogenetic protein 6 (BMP6) signaling in hepatocytes is a central transcriptional regulator of the iron hormone hepcidin that controls systemic iron balance. How iron levels are sensed to regulate hepcidin production is not known, but local induction of liver BMP6 expression by iron is proposed to have a critical role. To identify the cellular source of BMP6 responsible for hepcidin and iron homeostasis regulation, we generated mice with tissue-specific ablation of Bmp6 in different liver cell populations and evaluated their iron phenotype...
January 26, 2017: Blood
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