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Abstract

We recently characterized the role of HFE and TFR2 in the regulation of hepcidin as a complex using hepatoma cell lines and isolated primary hepatocytes as model systems (Cell Metab 2009;9:217–227). Our studies focused on the characterization of HFE and TfR2 in the direct regulation of hepcidin expression in hepatocytes. We agree that characterization of HFE and TFR2 in hepatocytes alone cannot completely account for their roles in iron homeostasis at the systematic level given the facts that the tissue expression profiles of HFE and TFR2 do not completely overlap and that the HFE and TFR2 expressed in hepatocytes only represent a fraction of each gene in the body as a whole. In addition to hepatocytes, HFE is expressed at lower levels in Kupffer cells in the liver (Blood 2004;103:1509–1514; J Hepatol 2003;39:308–314) as well as in the heart, pancreas, intestine, and other tissues (Nat Genet 1996;13:399–408). Although TFR2 is predominantly expressed in hepatocytes in the liver, TFR2 expression is also detected in immature erythroid cells (Oncogene 2002;21:7933–744). We look forward to reading about the extent to which mice lacking both Hfe and Tfr2 iron-overload and respond to dietary iron. We recently characterized the role of HFE and TFR2 in the regulation of hepcidin as a complex using hepatoma cell lines and isolated primary hepatocytes as model systems (Cell Metab 2009;9:217–227). Our studies focused on the characterization of HFE and TfR2 in the direct regulation of hepcidin expression in hepatocytes. We agree that characterization of HFE and TFR2 in hepatocytes alone cannot completely account for their roles in iron homeostasis at the systematic level given the facts that the tissue expression profiles of HFE and TFR2 do not completely overlap and that the HFE and TFR2 expressed in hepatocytes only represent a fraction of each gene in the body as a whole. In addition to hepatocytes, HFE is expressed at lower levels in Kupffer cells in the liver (Blood 2004;103:1509–1514; J Hepatol 2003;39:308–314) as well as in the heart, pancreas, intestine, and other tissues (Nat Genet 1996;13:399–408). Although TFR2 is predominantly expressed in hepatocytes in the liver, TFR2 expression is also detected in immature erythroid cells (Oncogene 2002;21:7933–744). We look forward to reading about the extent to which mice lacking both Hfe and Tfr2 iron-overload and respond to dietary iron. Hepcidin Regulation by HFE and TFR2: Is It Enough to Give a Hepatocyte a Complex?GastroenterologyVol. 137Issue 3PreviewGao J, Chen J, Kramer M, et al. (Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, OR; others). Interaction of the hereditary hemochromatosis protein HFE with Transferrin Receptor 2 is required for transferrin-induced hepcidin expression. Cell Metabolism 2009;9:217–227. Full-Text PDF