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Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D(3)-enhanced duodenal calcium transport in male mice Khuituan P; Teerapornpuntakit J; Wongdee K; Suntornsaratoon P; Konthapakdee N; Sangsaksri J; Sripong C; Krishnamra N; Charoenphandhu NAm J Physiol Endocrinol Metab 2012[Apr]; 302 (8): E903-13Despite 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)D(3)], FGF-23 probably compromised the 1,25(OH)(2)D(3)-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 mug/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 1-4 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)D(3)-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)D(3)-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.|*Intestinal Absorption/drug effects[MESH]|Animals[MESH]|Calbindins[MESH]|Calcitriol/*metabolism[MESH]|Calcium Channels/genetics/metabolism[MESH]|Calcium, Dietary/*metabolism[MESH]|Cell Polarity[MESH]|Duodenum/cytology/drug effects/*metabolism[MESH]|Fibroblast Growth Factor-23[MESH]|Fibroblast Growth Factors/genetics/*metabolism[MESH]|Gene Expression Regulation[MESH]|In Vitro Techniques[MESH]|Intestinal Mucosa/cytology/drug effects/*metabolism[MESH]|MAP Kinase Signaling System/drug effects[MESH]|Male[MESH]|Mice[MESH]|Mice, Inbred ICR[MESH]|Organ Specificity[MESH]|Protein Isoforms/genetics/metabolism[MESH]|Protein Kinase Inhibitors/pharmacology[MESH]|RNA, Messenger/metabolism[MESH]|Receptors, Fibroblast Growth Factor/antagonists & inhibitors/metabolism[MESH]|Recombinant Proteins/metabolism[MESH]|S100 Calcium Binding Protein G/genetics/metabolism[MESH]|TRPV Cation Channels/genetics/metabolism[MESH] |
