Is the iron donor lipocalin 2 implicated in the pathophysiology of hereditary hemochromatosis?
Under normal conditions, iron is taken up by the cells through the transferrin-mediated pathway. However, in hereditary hemochromatosis, a common iron-overloading disorder associated with mutations in the HFE gene, iron in plasma exceeds transferrin-binding capacity, and non-transferrin-bound iron (NTBI) appears in the circulation of patients with iron overload. NTBI can be taken up by hepatocytes through a transferrin-independent pathway. Lipocalin 2 (Lcn2), a secreted protein of the lipocalin family, has emerged as the mediator of an alternative, transferrin-independent pathway for cellular iron delivery. To evaluate the importance of Lcn2 in the pathogenesis of hepatic iron loading in Hfe knockout mice, we generated HfeLcn2 double-deficient mice. Our studies revealed that deletion of Lcn2 in Hfe-knockout mice does not influence hepatic iron accumulation in Hfe(-/-) mice, or their response to iron loading, as the phenotype of HfeLcn2(-/-) mice remained indistinguishable from that of Hfe(-/-) mice.


CONCLUSIONS
Lcn2 is not essential for iron delivery to hepatocytes in hemochromatosis.
Huang
Hua
H
Département de Médicine, Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Université de Montréal, Montréal, Québec, Canada.
Akira
Shizuo
S
Santos
Manuela M
MM
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D000071020:Hemochromatosis Protein; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*
D000209:Acute-Phase Proteins; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D000071068:Lipocalin-2; D054834:Lipocalins; D008565:Membrane Proteins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; D007501:Iron