Effect of erythropoietin on hepcidin expression in hemojuvelin-mutant mice
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20219396
DOI
10.1016/j.bcmd.2010.02.012
PII: S1079-9796(10)00068-9
Knihovny.cz E-resources
- MeSH
- Down-Regulation drug effects MeSH
- Erythropoietin pharmacology MeSH
- Erythropoiesis drug effects genetics MeSH
- Transcription, Genetic drug effects MeSH
- GPI-Linked Proteins MeSH
- Hepcidins MeSH
- Liver drug effects metabolism MeSH
- Antimicrobial Cationic Peptides biosynthesis genetics MeSH
- Bone Morphogenetic Protein 6 biosynthesis genetics MeSH
- Membrane Proteins deficiency genetics physiology MeSH
- RNA, Messenger biosynthesis MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Polysaccharides pharmacology toxicity MeSH
- Iron Overload chemically induced metabolism MeSH
- Hemochromatosis Protein MeSH
- Gene Expression Regulation drug effects MeSH
- Recombinant Proteins MeSH
- Ferric Compounds pharmacology toxicity MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Bmp6 protein, mouse MeSH Browser
- epoetin beta MeSH Browser
- Erythropoietin MeSH
- GPI-Linked Proteins MeSH
- Hamp protein, mouse MeSH Browser
- Hepcidins MeSH
- HJV protein, mouse MeSH Browser
- iron polyisomaltosate MeSH Browser
- Antimicrobial Cationic Peptides MeSH
- Bone Morphogenetic Protein 6 MeSH
- Membrane Proteins MeSH
- RNA, Messenger MeSH
- Polysaccharides MeSH
- Hemochromatosis Protein MeSH
- Recombinant Proteins MeSH
- Ferric Compounds MeSH
Transcription of the hepcidin (Hamp) gene is controlled by iron stores and the rate of erythropoiesis. Functional hierarchy between these two stimuli has not yet been completely established. It is also not known whether the erythropoiesis-related downregulation of Hamp expression utilises the bone morphogenetic protein/hemojuvelin (Bmp/Hjv) pathway. Hemojuvelin-mutant (Hjv-/-) mice treated with erythropoietin (EPO) at 50IU/mouse/day for three days displayed marked decrease in Hamp mRNA, demonstrating that hemojuvelin is not an indispensable component in EPO-induced Hamp gene downregulation. Irradiation of Hjv-/- mice prevented the EPO-induced decrease of Hamp mRNA, highlighting the role of erythropoiesis in Hamp gene regulation by EPO. After a single injection of EPO, Hamp mRNA levels were not significantly changed at 6h, but decreased at 10 and 24h. Chronic bleeding decreased hepatic Bmp6 mRNA levels; however, repeated EPO treatment did not change Bmp6 mRNA, suggesting that the erythropoietic regulator(s) act independently of the Bmp/Hjv pathway. Pretreatment of C57BL/6 mice with iron (5mg/mouse) almost completely inhibited the EPO-induced decrease of Hamp mRNA. This result suggests that administration of EPO to patients with transfusional iron overload is probably not associated with the risk of additional absorption of substantial amounts of iron from the diet.
References provided by Crossref.org
Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2
Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies in Mask Mice
Effect of iron overload and iron deficiency on liver hemojuvelin protein
