Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D<inf>3</inf>-enhanced duodenal calcium transport in male mice
Despite being widely recognized as the important bone-derived phosphaturic hormone, whether fibroblast growth factor (FGF)-23 modulated intestinal calcium absorption remained elusive. Since FGF-23 could reduce the circulating level of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D3], FGF-23 probably compro...
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th-mahidol.137572018-06-11T12:12:35Z Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D<inf>3</inf>-enhanced duodenal calcium transport in male mice Pissared Khuituan Jarinthorn Teerapornpuntakit Kannikar Wongdee Panan Suntornsaratoon Nipaporn Konthapakdee Jintana Sangsaksri Chanakarn Sripong Nateetip Krishnamra Narattaphol Charoenphandhu Mahidol University Burapha University Biochemistry, Genetics and Molecular Biology Medicine Despite being widely recognized as the important bone-derived phosphaturic hormone, whether fibroblast growth factor (FGF)-23 modulated intestinal calcium absorption remained elusive. Since FGF-23 could reduce the circulating level of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D3], FGF-23 probably compromised the 1,25(OH) 2 D3 induced intestinal calcium absorption. FGF-23 may also exert an inhibitory action directly through FGF receptors (FGFR) in the intestinal cells. Herein, we demonstrated by Ussing chamber technique that male mice administered 1 μg/kg 1,25(OH) 2 D 3 sc daily for 3 days exhibited increased duodenal calcium absorption, which was abolished by concurrent intravenous injection of recombinant mouse FGF-23. This FGF-23 administration had no effect on the background epithelial electrical properties, i.e., short-circuit current, transepithelial potential difference, and resistance. Immunohistochemical evidence of protein expressions of FGFR isoforms 14 in mouse duodenal epithelial cells suggested a possible direct effect of FGF-23 on the intestine. This was supported by the findings that FGF-23 directly added to the serosal compartment of the Ussing chamber and completely abolished the 1,25(OH) 2 D3-induced calcium absorption in the duodenal tissues taken from the 1,25(OH) 2 D 3 -treated mice. However, direct FGF-23 exposure did not decrease the duodenal calcium absorption without 1,25(OH) 2 D 3 preinjection. The observed FGF-23 action was mediated by MAPK/ERK, p38 MAPK, and PKC. Quantitative real-time PCR further showed that FGF-23 diminished the 1,25(OH) 2 D3-induced upregulation of TRPV5, TRPV6, and calbindin-D 9k , but not PMCA 1b expression in the duodenal epithelial cells. In conclusion, besides being a phosphatonin, FGF-23 was shown to be a novel calcium-regulating hormone that acted directly on the mouse intestine, thereby compromising the 1,25(OH) 2 D 3 -induced calcium absorption. © 2012 the American Physiological Society. 2018-06-11T04:37:43Z 2018-06-11T04:37:43Z 2012-04-15 Article American Journal of Physiology - Endocrinology and Metabolism. Vol.302, No.8 (2012) 10.1152/ajpendo.00620.2011 15221555 01931849 2-s2.0-84859470865 https://repository.li.mahidol.ac.th/handle/123456789/13757 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84859470865&origin=inward |
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Biochemistry, Genetics and Molecular Biology Medicine Pissared Khuituan Jarinthorn Teerapornpuntakit Kannikar Wongdee Panan Suntornsaratoon Nipaporn Konthapakdee Jintana Sangsaksri Chanakarn Sripong Nateetip Krishnamra Narattaphol Charoenphandhu Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D<inf>3</inf>-enhanced duodenal calcium transport in male mice |
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Despite being widely recognized as the important bone-derived phosphaturic hormone, whether fibroblast growth factor (FGF)-23 modulated intestinal calcium absorption remained elusive. Since FGF-23 could reduce the circulating level of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D3], FGF-23 probably compromised the 1,25(OH) 2 D3 induced intestinal calcium absorption. FGF-23 may also exert an inhibitory action directly through FGF receptors (FGFR) in the intestinal cells. Herein, we demonstrated by Ussing chamber technique that male mice administered 1 μg/kg 1,25(OH) 2 D 3 sc daily for 3 days exhibited increased duodenal calcium absorption, which was abolished by concurrent intravenous injection of recombinant mouse FGF-23. This FGF-23 administration had no effect on the background epithelial electrical properties, i.e., short-circuit current, transepithelial potential difference, and resistance. Immunohistochemical evidence of protein expressions of FGFR isoforms 14 in mouse duodenal epithelial cells suggested a possible direct effect of FGF-23 on the intestine. This was supported by the findings that FGF-23 directly added to the serosal compartment of the Ussing chamber and completely abolished the 1,25(OH) 2 D3-induced calcium absorption in the duodenal tissues taken from the 1,25(OH) 2 D 3 -treated mice. However, direct FGF-23 exposure did not decrease the duodenal calcium absorption without 1,25(OH) 2 D 3 preinjection. The observed FGF-23 action was mediated by MAPK/ERK, p38 MAPK, and PKC. Quantitative real-time PCR further showed that FGF-23 diminished the 1,25(OH) 2 D3-induced upregulation of TRPV5, TRPV6, and calbindin-D 9k , but not PMCA 1b expression in the duodenal epithelial cells. In conclusion, besides being a phosphatonin, FGF-23 was shown to be a novel calcium-regulating hormone that acted directly on the mouse intestine, thereby compromising the 1,25(OH) 2 D 3 -induced calcium absorption. © 2012 the American Physiological Society. |
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Mahidol University Pissared Khuituan Jarinthorn Teerapornpuntakit Kannikar Wongdee Panan Suntornsaratoon Nipaporn Konthapakdee Jintana Sangsaksri Chanakarn Sripong Nateetip Krishnamra Narattaphol Charoenphandhu |
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Pissared Khuituan Jarinthorn Teerapornpuntakit Kannikar Wongdee Panan Suntornsaratoon Nipaporn Konthapakdee Jintana Sangsaksri Chanakarn Sripong Nateetip Krishnamra Narattaphol Charoenphandhu |
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Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D<inf>3</inf>-enhanced duodenal calcium transport in male mice |
title_short |
Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D<inf>3</inf>-enhanced duodenal calcium transport in male mice |
title_full |
Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D<inf>3</inf>-enhanced duodenal calcium transport in male mice |
title_fullStr |
Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D<inf>3</inf>-enhanced duodenal calcium transport in male mice |
title_full_unstemmed |
Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D<inf>3</inf>-enhanced duodenal calcium transport in male mice |
title_sort |
fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin d<inf>3</inf>-enhanced duodenal calcium transport in male mice |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/13757 |
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