Regulation of gene expression of epithelial calcium channels in intestine and kidney of mice by 1alpha,25-dihydroxyvitamin D3.
In wild-type (VDR(+/+)) mice, ECaC2 expression was confirmed in the intestine and kidney, while ECaC1 expression was exclusively confined to the kidney. Both mRNAs expression of ECaC1 and ECaC2 in the kidney and ECaC2 mRNA expression in the intestine increased time- and dose-dependently in response to 1alpha,25(OH)(2)D(3) injection in VDR(+/+) mice, but not in VDR(-/-) mice. The mRNA levels of ECaC2 in the intestine of VDR(-/-) mice were remarkably reduced when compared to VDR(+/+) mice, while no significant differences were observed in both mRNA levels of ECaC1 and ECaC2 in the kidney between VDR(+/+) mice and VDR(-/-) mice. In the primary renal tubular cells (PRTC) isolated from VDR(+/+) mice, both ECaCs mRNA expression increased in response to 1alpha,25(OH)(2)D(3) treatment, but not in the PRTC of VDR(-/-) mice. PTH increased both ECaCs mRNA expression in the PRTC of VDR(+/+) mice. These results suggest that 1alpha,25(OH)(2)D(3) directly modulates the gene expression of ECaC1 and ECaC2 together with PTH in the kidney of mice. 1alpha,25(OH)(2)D(3) also modulates the gene expression of ECaC2 in the intestine of mice, however, further studies are needed to elucidate the direct action of 1alpha,25(OH)(2)D(3) on the expression of ECaC2 in the intestine.
Okano
Toshio
T
Department of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan. t-okano@kobepharma-u.ac.jp
Tsugawa
Naoko
N
Morishita
Atsushi
A
Kato
Shigeaki
S
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D015220:Calcium Channels / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels
D015220:Calcium Channels; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; C446923:Trpv6 protein, mouse; D002117:Calcitriol