Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations. Issue 12 (16th July 2021)

• Record Type: Journal Article
• Authors: Katsarou, Angeliki; Gkouvatsos, Konstantinos; Fillebeen, Carine; Pantopoulos, Kostas
• Is Part Of: Hepatology communications. Volume 5:Issue 12(2021)
• Page Start: 2139
• Page End: 2150
• Publication Date: 2021-07-16
• Subjects: Hepatology -- Periodicals; Liver -- Diseases -- Periodicals; Liver Diseases; Gastroenterology; Periodicals; Fulltext; Internet Resources; Periodicals; 616.36
• DOI: 10.1002/hep4.1780
• Languages: English
• ISSNs: 2471-254X

Abstract

Abstract : Hepcidin is a liver‐derived peptide hormone that limits iron egress from tissues to the bloodstream. It operates by binding to the iron exporter ferroportin, which blocks iron transport and tags ferroportin for degradation. Genetic hepcidin inactivation leads to hereditary hemochromatosis, a disease of iron overload. We used wild‐type and Hjv‐/‐ mice, a model of hemochromatosis, to examine the expression of ferroportin and other proteins of iron metabolism in hepcidin target tissues. The animals were previously subjected to dietary iron manipulations. In Hjv‐/‐ mice, hepcidin messenger RNA correlated significantly with hepatic iron load (r = 0.8211, P < 0.001), but was substantially lower compared with wild‐type controls. Duodenal ferroportin and divalent metal transporter 1 (DMT1), as well as splenic and hepatic ferroportin, were overexpressed in these animals. A high‐iron diet (2% carbonyl iron) suppressed duodenal DMT1 levels in both wild‐type and Hjv‐/‐ mice; however, it did not affect duodenal ferroportin expression in Hjv‐/‐ mice, and only reduced it in wild‐type mice. In contrast, the high‐iron diet decreased splenic ferroportin exclusively in Hjv‐/‐ mice, whereas it induced hepatic ferroportin exclusively in wild‐type mice. Conclusion: Our data show that dietary iron differentially affects ferroportin expression in mouse tissues and are consistent with hepcidin‐dependent and hepcidin‐independent mechanisms for ferroportin regulation. In the Hjv‐/‐ mouse model of hemochromatosis, duodenal ferroportin remains unresponsive to iron but DMT1 is appropriately iron‐regulated. Abstract : Ferroportin is differentially regulated by dietary iron in the spleen, liver and duodenum of wild type and Hjv‐/‐ mice.Overexpressed duodenal ferroportin does not respond to dietary iron in Hjv‐/‐ mice.Duodenal DMT1 is appropriately iron‐regulated in both wild‐type and Hjv‐/‐ mice.image