Genetic background influences hepcidin response to iron imbalance in a mouse model of hemolytic anemia (Congenital erythropoietic porphyria)
| Autor: | Emmanuel Richard, Pierre Costet, Said Lyoumi, Cécile Ged, Thibaud Lefebvre, Magalie Lalanne, Hervé Puy, Zoubida Karim, Hubert de Verneuil, François Moreau-Gaudry, Isabelle Lamrissi-Garcia, Jean-Marc Blouin, Sarah Millot, Laurent Gouya |
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| Přispěvatelé: | Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7) |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Hemolytic anemia Male medicine.medical_specialty Iron Overload Porphyrins Anemia Iron Porphyria Erythropoietic Ferroportin Biophysics Congenic Congenital erythropoietic porphyria Mice Inbred Strains Biochemistry Hemolysis 03 medical and health sciences 0302 clinical medicine Hepcidins Hepcidin hemic and lymphatic diseases Internal medicine medicine Animals Molecular Biology Cation Transport Proteins ComputingMilieux_MISCELLANEOUS Mice Inbred BALB C biology business.industry Cell Biology medicine.disease Uroporphyrinogen III Synthetase 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics 030220 oncology & carcinogenesis biology.protein Erythropoiesis Female business |
| Zdroj: | Biochemical and Biophysical Research Communications Biochemical and Biophysical Research Communications, Elsevier, 2019, 520 (2), pp.297-303. ⟨10.1016/j.bbrc.2019.09.141⟩ |
| ISSN: | 1090-2104 0006-291X |
| DOI: | 10.1016/j.bbrc.2019.09.141⟩ |
| Popis: | Clinical severity is heterogeneous among patients suffering from congenital erythropoietic porphyria (CEP) suggesting a modulation of the disease (UROS deficiency) by environmental factors and modifier genes. A KI model of CEP due to a missense mutation of UROS gene present in human has been developed on 3 congenic mouse strains (BALB/c, C57BL/6, and 129/Sv) in order to study the impact of genetic background on disease severity. To detect putative modifiers of disease expression in congenic mice, hematologic data, iron parameters, porphyrin content and tissue samples were collected. Regenerative hemolytic anemia, a consequence of porphyrin excess in RBCs, had various expressions: 129/Sv mice were more hemolytic, BALB/c had more regenerative response to anemia, C57BL/6 were less affected. Iron status and hemolysis level were directly related: C57BL/6 and BALB/c had moderate hemolysis and active erythropoiesis able to reduce iron overload in the liver, while, 129/Sv showed an imbalance between iron release due to hemolysis and erythroid use. The negative control of hepcidin on the ferroportin iron exporter appeared strain specific in the CEP mice models tested. Full repression of hepcidin was observed in BALB/c and 129/Sv mice, favoring parenchymal iron overload in the liver. Unchanged hepcidin levels in C57BL/6 resulted in retention of iron predominantly in reticuloendothelial tissues. These findings open the field for potential therapeutic applications in the human disease, of hepcidin agonists and iron depletion in chronic hemolytic anemia. |
| Databáze: | OpenAIRE |
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