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 Printable version |
Hemojuvelin and iron related diseases |
Hépato-Gastro. Volume 16, Number 3, 173-9, mai-juin 2009, Mini-revue
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 Résumé
Article gratuit
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Author(s) : Olivier Loréal, Lenaïck Détivaud, Edouard Bardou-Jacquet, Marie-Laure Island, Anne-Marie Jouanolle, Pierre Brissot |
Summary : Hemojuvelin is a protein playing a major role in the control of hepcidin expression. Therefore, hemojuvelin impacts strongly iron homeostasis due to the key function of hepcidin for maintaining adequate plasmatic iron bioavailability. Expressed on the hepatocyte cell membrane, hemojuvelin plays a role of bone morphogenetic proteins (BMPs) co-receptor, and thus participates to the signal transduction related to the interaction between BMPs which implicates the BMP/SMAD pathway. Hepcidin expression is induced through involvement of the BMP-responsive elements located within the hepcidin gene promoter. Hemojuvelin soluble form, produced by hepatocytes and striated muscles, could modulate, through competition with BMP receptors, the biological efficiency of the anchored form of hemojuvelin. On one hand HJV gene homozygous mutations are involved in the development of severe forms of hemochromatosis occurring frequently before 30 years old. They are linked to low levels of hepcidin due to the dysfunction in the HJV/BMP/SMAD pathway. Heterozygous mutations of HJV gene may modulate the severity of other genetic iron overload syndromes, especially those related to C282Y HFE mutations. On the other hand, mutations in the TMPRSS6 (matriptase 2) gene, which may cleave the HJV protein anchored in cell membrane, facilitate its expression and thus induce an hyperactivity of BMP/SMAD pathway. In turn, hepcidin expression is increased, thus favouring the development of serum iron parameters decrease and of microcytic anaemia, similar to those found in chronic inflammatory diseases and do not respond to iron supplementation. |
Keywords : hemojuvelin, iron metabolism, hepcidin, hemochromatosis, anaemia |
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