PMID- 29282249
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 32
IP  - 4
DP  - 2018 Apr
TI  - Phosphate-dependent luminal ATP metabolism regulates transcellular calcium 
      transport in intestinal epithelial cells.
PG  - 1903-1915
LID - 10.1096/fj.201700631R [doi]
AB  - Extracellular low phosphate strongly enhances intestinal calcium absorption 
      independently of active vitamin D [1,25(OH)(2)D(3)] signaling, but the underlying 
      mechanisms remain poorly characterized. To elucidate the phosphate-dependent 
      regulation of calcium transport, we investigated part of the enteral environment 
      that is involved in 1,25(OH)(2)D(3)-independent calcium absorption, which 
      responds to dietary phosphate levels in mice that lack intestinal vitamin D 
      receptor ( Vdr) activity. Impaired calcium absorption in intestinal Vdr-null mice 
      was improved by dietary phosphate restriction. Accordingly, calcium transport in 
      cultured intestinal epithelial cells was increased when the apical side was 
      exposed to low phosphate levels (0.5 mM) compared with normal or high phosphate 
      levels (1.0 or 5.0 mM, respectively). Mechanistically, low phosphate increased 
      ATP in the apical side medium and allowed calcium entry into epithelial cells via 
      the P2X7 purinoreceptor, which results in increased calcium transport. We found 
      that luminal ATP was regulated by the release and degradation of ATP at the 
      epithelium, and phosphate restriction increased ATP release from epithelial cells 
      via connexin-43 hemichannels. Furthermore, ATP degradation by ectonucleotide 
      pyrophosphatase-1 was reduced, which was caused by the reduction of the MAPK 
      cascade. These findings indicate that luminal ATP metabolism regulates 
      transcellular calcium transport in the intestine by an 
      1,25(OH)(2)D(3)-independent mechanism in response to dietary phosphate 
      levels.-Uekawa, A., Yamanaka, H., Lieben, L., Kimira, Y., Uehara, M., Yamamoto, 
      Y., Kato, S., Ito, K., Carmeliet, G., Masuyama, R. Phosphate-dependent luminal 
      ATP metabolism regulates transcellular calcium transport in intestinal epithelial 
      cells.
FAU - Uekawa, Atsushi
AU  - Uekawa A
AD  - Department of Molecular Bone Biology, Graduate School of Biomedical Sciences, 
      Nagasaki University, Nagasaki, Japan.
FAU - Yamanaka, Hitoki
AU  - Yamanaka H
AD  - Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.
FAU - Lieben, Liesbet
AU  - Lieben L
AD  - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
FAU - Kimira, Yoshifumi
AU  - Kimira Y
AD  - Department of Nutritional Science, Tokyo University of Agriculture, Tokyo, Japan.
FAU - Uehara, Mariko
AU  - Uehara M
AD  - Department of Nutritional Science, Tokyo University of Agriculture, Tokyo, Japan.
FAU - Yamamoto, Yoko
AU  - Yamamoto Y
AD  - Surgical Oncology and Vascular Surgery, University of Tokyo, Tokyo, Japan.
FAU - Kato, Shigeaki
AU  - Kato S
AD  - Research Institute of Innovative Medicine, Tokiwa Foundation, Iwaki, Fukushima, 
      Japan.
FAU - Ito, Kosei
AU  - Ito K
AD  - Department of Molecular Bone Biology, Graduate School of Biomedical Sciences, 
      Nagasaki University, Nagasaki, Japan.
FAU - Carmeliet, Geert
AU  - Carmeliet G
AD  - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
FAU - Masuyama, Ritsuko
AU  - Masuyama R
AD  - Department of Molecular Bone Biology, Graduate School of Biomedical Sciences, 
      Nagasaki University, Nagasaki, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180105
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Connexin 43)
RN  - 0 (Phosphates)
RN  - 1406-16-2 (Vitamin D)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.6.1.- (Pyrophosphatases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Animals
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - Connexin 43/metabolism
MH  - Female
MH  - Intestinal Absorption
MH  - Intestinal Mucosa/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Phosphates/metabolism
MH  - Pyrophosphatases/metabolism
MH  - *Transcytosis
MH  - Vitamin D/metabolism
OTO - NOTNLM
OT  - Cx43
OT  - ENPP1
OT  - extracellular phosphate
EDAT- 2017/12/29 06:00
MHDA- 2018/12/12 06:00
CRDT- 2017/12/29 06:00
PHST- 2017/12/29 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2017/12/29 06:00 [entrez]
AID - fj.201700631R [pii]
AID - 10.1096/fj.201700631R [doi]
PST - ppublish
SO  - FASEB J. 2018 Apr;32(4):1903-1915. doi: 10.1096/fj.201700631R. Epub 2018 Jan 5.