Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations

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...

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Autores principales:	Angeliki Katsarou, Konstantinos Gkouvatsos, Carine Fillebeen, Kostas Pantopoulos
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/784ef1e3ba9a41588b921c36f160bff0
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spelling	oai:doaj.org-article:784ef1e3ba9a41588b921c36f160bff02021-11-30T13:39:17ZTissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations2471-254X10.1002/hep4.1780https://doaj.org/article/784ef1e3ba9a41588b921c36f160bff02021-12-01T00:00:00Zhttps://doi.org/10.1002/hep4.1780https://doaj.org/toc/2471-254XHepcidin 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.Angeliki KatsarouKonstantinos GkouvatsosCarine FillebeenKostas PantopoulosWileyarticleDiseases of the digestive system. GastroenterologyRC799-869ENHepatology Communications, Vol 5, Iss 12, Pp 2139-2150 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Diseases of the digestive system. Gastroenterology RC799-869 Angeliki Katsarou Konstantinos Gkouvatsos Carine Fillebeen Kostas Pantopoulos Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations
description	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.
format	article
author	Angeliki Katsarou Konstantinos Gkouvatsos Carine Fillebeen Kostas Pantopoulos
author_facet	Angeliki Katsarou Konstantinos Gkouvatsos Carine Fillebeen Kostas Pantopoulos
author_sort	Angeliki Katsarou
title	Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations
title_short	Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations
title_full	Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations
title_fullStr	Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations
title_full_unstemmed	Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations
title_sort	tissue‐specific regulation of ferroportin in wild‐type and hjv‐/‐ mice following dietary iron manipulations
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/784ef1e3ba9a41588b921c36f160bff0
work_keys_str_mv	AT angelikikatsarou tissuespecificregulationofferroportininwildtypeandhjvmicefollowingdietaryironmanipulations AT konstantinosgkouvatsos tissuespecificregulationofferroportininwildtypeandhjvmicefollowingdietaryironmanipulations AT carinefillebeen tissuespecificregulationofferroportininwildtypeandhjvmicefollowingdietaryironmanipulations AT kostaspantopoulos tissuespecificregulationofferroportininwildtypeandhjvmicefollowingdietaryironmanipulations
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Tissue‐Specific Regulation of Ferroportin in Wild‐Type and Hjv‐/‐ Mice Following Dietary Iron Manipulations

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