The effects of Vitamin D metabolites on expression of genes for calcium transporters in human duodenum.
The role of Vitamin D in the regulation of calcium absorption in the intestine is well recognized but the mechanisms of the effects on human genes are surprisingly poorly understood. We have determined the expression of transcripts of the apical membrane calcium transporter TRPV6, the cytoplasmic calcium binding protein calbindin-D9k, the basolateral plasma membrane Ca(2+)-ATPase (PMCA1) and the Vitamin D receptor (VDR) in normal endoscopic duodenal mucosal biopsies using quantitative real-time RT-PCR and related baseline expression to Vitamin D metabolites. TRPV6 transcript levels have been shown to be significantly correlated with serum 1,25(OH)(2)D levels in men, but not overall in women, where negative effects of age predominate. TRPV6 and VDR expression were significantly related in both men and women, but were significantly lower in older women. Associations with bone mineral density and fractional calcium absorption were also studied. In a second series of subjects, duodenal biopsies were incubated in organ culture for 6h with Vitamin D metabolites. TRPV6 expression was significantly increased by 1,25(OH)(2)D(3) (10(-9)mol/l) as was PMCA1 to a much smaller extent. TRPV6 expression also increased with 25(OH)D(3). CYP27B1 expression was found in all samples, and CYP24 transcripts were detected after incubation with 1,25(OH)(2)D(3) or 25(OH)D(3).
Walters
Julian R F
JR
Department of Gastroenterology, Hammersmith Hospital, Imperial College London, London W12 0NN, UK. julian.walters@imperial.ac.uk
Balesaria
Sara
S
Khair
Umma
U
Sangha
Sonia
S
Banks
Linda
L
Berry
Jacqueline L
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000378:metabolism* / Q000494:pharmacology*
D015220:Calcium Channels; D014807:Vitamin D; D002118:Calcium