Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.

Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transpo...

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Autores principales:	Supathra Phoaubon, Kornkamon Lertsuwan, Jarinthorn Teerapornpuntakit, Narattaphol Charoenphandhu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5db057ce39574f8b8565c58027ac6948
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spelling	oai:doaj.org-article:5db057ce39574f8b8565c58027ac69482021-12-02T20:19:16ZHepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.1932-620310.1371/journal.pone.0258433https://doaj.org/article/5db057ce39574f8b8565c58027ac69482021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258433https://doaj.org/toc/1932-6203Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transport. However, whether this effect could be replicated in other conditions is not known. Therefore, this study aimed to investigate the effects of hepcidin on iron and calcium uptake ability under physiological, iron uptake stimulation and calcium uptake suppression. To investigate the potential mechanism, effects of hepcidin on the expression of iron and calcium transporter and transport-associated protein in Caco-2 cells were also determined. Our results showed that intestinal cell iron uptake was significantly increased by ascorbic acid together with ferric ammonium citrate (FAC), but this phenomenon was suppressed by hepcidin. Interestingly, hepcidin significantly increased calcium uptake under physiological condition but not under iron uptake stimulation. While hepcidin significantly suppressed the expression of iron transporter, it had no effect on calcium transporter expression. This indicated that hepcidin-induced intestinal cell calcium uptake did not occur through the stimulation of calcium transporter expression. On the other hand, 1,25(OH)2D3 effectively induced intestinal cell calcium uptake, but it did not affect intestinal cell iron uptake or iron transporter expression. The 1,25(OH)2D3-induced intestinal cell calcium uptake was abolished by 12 mM CaCl2; however, hepcidin could not rescue intestinal cell calcium uptake suppression by CaCl2. Taken together, our results showed that hepcidin could effectively and concurrently induce intestinal cell calcium uptake while reducing intestinal cell iron uptake under physiological and iron uptake stimulation conditions, suggesting its therapeutic potential for inactive calcium absorption, particularly in thalassemic patients or patients who did not adequately respond to 1,25(OH)2D3.Supathra PhoaubonKornkamon LertsuwanJarinthorn TeerapornpuntakitNarattaphol CharoenphandhuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258433 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Supathra Phoaubon Kornkamon Lertsuwan Jarinthorn Teerapornpuntakit Narattaphol Charoenphandhu Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
description	Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transport. However, whether this effect could be replicated in other conditions is not known. Therefore, this study aimed to investigate the effects of hepcidin on iron and calcium uptake ability under physiological, iron uptake stimulation and calcium uptake suppression. To investigate the potential mechanism, effects of hepcidin on the expression of iron and calcium transporter and transport-associated protein in Caco-2 cells were also determined. Our results showed that intestinal cell iron uptake was significantly increased by ascorbic acid together with ferric ammonium citrate (FAC), but this phenomenon was suppressed by hepcidin. Interestingly, hepcidin significantly increased calcium uptake under physiological condition but not under iron uptake stimulation. While hepcidin significantly suppressed the expression of iron transporter, it had no effect on calcium transporter expression. This indicated that hepcidin-induced intestinal cell calcium uptake did not occur through the stimulation of calcium transporter expression. On the other hand, 1,25(OH)2D3 effectively induced intestinal cell calcium uptake, but it did not affect intestinal cell iron uptake or iron transporter expression. The 1,25(OH)2D3-induced intestinal cell calcium uptake was abolished by 12 mM CaCl2; however, hepcidin could not rescue intestinal cell calcium uptake suppression by CaCl2. Taken together, our results showed that hepcidin could effectively and concurrently induce intestinal cell calcium uptake while reducing intestinal cell iron uptake under physiological and iron uptake stimulation conditions, suggesting its therapeutic potential for inactive calcium absorption, particularly in thalassemic patients or patients who did not adequately respond to 1,25(OH)2D3.
format	article
author	Supathra Phoaubon Kornkamon Lertsuwan Jarinthorn Teerapornpuntakit Narattaphol Charoenphandhu
author_facet	Supathra Phoaubon Kornkamon Lertsuwan Jarinthorn Teerapornpuntakit Narattaphol Charoenphandhu
author_sort	Supathra Phoaubon
title	Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_short	Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_full	Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_fullStr	Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_full_unstemmed	Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_sort	hepcidin induces intestinal calcium uptake while suppressing iron uptake in caco-2 cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5db057ce39574f8b8565c58027ac6948
work_keys_str_mv	AT supathraphoaubon hepcidininducesintestinalcalciumuptakewhilesuppressingironuptakeincaco2cells AT kornkamonlertsuwan hepcidininducesintestinalcalciumuptakewhilesuppressingironuptakeincaco2cells AT jarinthornteerapornpuntakit hepcidininducesintestinalcalciumuptakewhilesuppressingironuptakeincaco2cells AT narattapholcharoenphandhu hepcidininducesintestinalcalciumuptakewhilesuppressingironuptakeincaco2cells
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Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.

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