Anemia upregulates lipocalin 2 in the liver and serum.
Lipocalin 2 (Lcn2), a mammalian protein that is expressed and secreted in various pathologic states, binds siderophores, which are high-affinity iron chelators. Besides its role in limiting iron availability to pathogens in the setting of bacterial infection, Lcn2:siderophore complexes can also deliver iron to cells. In this study, we examined Lcn2 regulation in the liver of mice in situations of increased iron utilization, namely, during anemia. Anemia induced by phlebotomy, iron deprivation, or phenylhydrazine treatment was associated with upregulation of Lcn2 gene expression in the liver and elevation of serum Lcn2 protein levels. We further explored the participation of several factors known to co-occur during anemia, including hypoxia, changes in iron levels, and erythropoietic drive, in the regulation of Lcn2 by anemia. We found that hypoxia, but not iron or erythropoietin, caused an induction of Lcn2 expression. The upregulation of Lcn2 levels by anemia and hypoxia, which is not directly mediated by iron or erythropoietin, suggests a possible physiological role for Lcn2 during increased iron utilization and mobilization from stores.
Centre de recherche, Centre Hospitalier de l'Université de Montréal (CHUM)-Hôpital Nôtre-Dame and Département de Médicine, Université de Montréal, Montréal, Québec, Canada.
Wenlei
W
Jiang
Marco
M
Constante
Manuela M
MM
Santos
D000209:Acute-Phase Proteins / Q000032:analysis* / Q000235:genetics; D000740:Anemia / Q000378:metabolism*; D000818:Animals; D004921:Erythropoietin; D005786:Gene Expression Regulation; D000860:Hypoxia; D007501:Iron; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis* / Q000097:blood / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D015513:Oncogene Proteins / Q000032:analysis* / Q000097:blood / Q000235:genetics; D015854:Up-Regulation
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D004921:Erythropoietin; C071332:Lcn2 protein, mouse; D007501:Iron