title: Fibroblast growth factor-23 negates 1,25(OH)2D3-induced intestinal calcium transport by reducing the transcellular and paracellular calcium fluxes.
abstract: The calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been known to stimulate intestinal calcium transport via both transcellular and paracellular pathways. Recently, we reported that the 1,25(OH)2D3-enhanced calcium transport in the mouse duodenum could be abolished by fibroblast growth factor (FGF)-23, but the targeted calcium transport pathway has been elusive. Herein, the 1,25(OH)2D3-enhanced calcium transport was markedly inhibited by FGF-23 and inhibitors of the basolateral calcium transporters, NCX1 and PMCA1b, suggesting the negative effect of FGF-23 on the transcellular calcium transport. Similar results could be observed in the intestinal epithelium-like Caco-2 monolayer. Although the Arrhenius plot indicated that FGF-23 decreased the potential barrier (e.g., activation energy) of the paracellular calcium movement, FGF-23 was found to modestly decrease the 1,25(OH)2D3-enhanced paracellular calcium transport and calcium permeability. Moreover, FGF-23 affected the 1,25(OH)2D3-induced change in duodenal water permeability as determined by tritiated water, but both 1,25(OH)2D3 and FGF-23 were without effects on the transepithelial fluxes of paracellular markers, (3)H-mannitol and (14)C-polyethylene glycol. It could be concluded that FGF-23 diminished the 1,25(OH)2D3-enhanced calcium absorption through the transcellular and paracellular pathways. Our findings have thus corroborated the presence of a bone-kidney-intestinal axis of FGF-23/vitamin D system in the regulation of calcium homeostasis.
authors.affiliation: Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Pissared
authors.initials: P
authors.lastname: Khuituan
authors.forename: Kannikar
authors.initials: K
authors.lastname: Wongdee
authors.forename: Walailuk
authors.initials: W
authors.lastname: Jantarajit
authors.forename: Panan
authors.initials: P
authors.lastname: Suntornsaratoon
authors.forename: Nateetip
authors.initials: N
authors.lastname: Krishnamra
authors.forename: Narattaphol
authors.initials: N
authors.lastname: Charoenphandhu
mesh_terms: D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D010539:Permeability; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; C499849:NCX1 protein, mouse; D019831:Sodium-Calcium Exchanger; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium
keywords: Arrhenius plot; Calcium permeability; Paracellular transport; Transcellular transport; Ussing chamber