Figure 6. Hepatic Expression of Hamp and Bmp6 mRNA in Slc39a14^−/− Mice with Genetic or Dietary Iron Overload.

Relative expression of hepcidin (Hamp) and Bmp6 mRNA was measured in (A) WT, Slc39a14^−/−, Hfe^−/−, and Hfe^−/−;Slc39a14^−/− mice at 4 wk of age (n = 7–9 per group), (B) WT, Slc39a14^−/−, Hfe2^−/−, and Hfe2^−/−;Slc39a14^−/− mice at 6 wk of age (n = 4–10 per group), and (C) WT-FeC, Slc39a14^−/−-FeC, WT-FeO and Slc39a14^−/−-FeO mice at 7 wk of age (n = 6 per group). Transcript levels were normalized to those of Rpl13a. All data are shown as the mean ± SEM. Means without a common superscript differ significantly (p < 0.01). (D) Proposed role of SLC39A14 in iron loading of the liver and pancreas and effect of SLC39A14 deficiency on hepatic BMP6 regulation. In iron overload, the iron-binding capacity of plasma transferrin (gray ovals) becomes exceeded, giving rise to NTBI, which loads into hepatocytes and pancreatic acinar cells via SLC39A14. In iron overload with SLC39A14 deficiency, iron does not load in hepatocytes or acinar cells, but can accumulate in nonparenchymal cells of the liver (endothelial cells (EC), hepatic stellate cells (HSC), and Kupffer cells (KC)) and collagen fibers in the pancreas. That hepatic BMP6 expression can be upregulated in iron overload with SLC39A14 deficiency (A, B, C) suggests that BMP6 expression is regulated by SLC39A14-independent iron loading of nonparenchymal cells. See also Figure S6.