RRC ID |
62796
|
著者 |
Masuda M, Yamamoto H, Takei Y, Nakahashi O, Adachi Y, Ohnishi K, Ohminami H, Yamanaka-Okumura H, Sakaue H, Miyazaki M, Takeda E, Taketani Y.
|
タイトル |
All-trans retinoic acid reduces the transcriptional regulation of intestinal sodium-dependent phosphate co-transporter gene (Npt2b).
|
ジャーナル |
Biochem J
|
Abstract |
Inorganic phosphate (Pi) homeostasis is regulated by intestinal absorption via type II sodium-dependent co-transporter (Npt2b) and by renal reabsorption via Npt2a and Npt2c. Although we previously reported that vitamin A-deficient (VAD) rats had increased urine Pi excretion through the decreased renal expression of Npt2a and Npt2c, the effect of vitamin A on the intestinal Npt2b expression remains unclear. In this study, we investigated the effects of treatment with all-trans retinoic acid (ATRA), a metabolite of vitamin A, on the Pi absorption and the Npt2b expression in the intestine of VAD rats, as well as and the underlying molecular mechanisms. In VAD rats, the intestinal Pi uptake activity and the expression of Npt2b were increased, but were reduced by the administration of ATRA. The transcriptional activity of reporter plasmid containing the promoter region of the rat Npt2b gene was reduced by ATRA in NIH3T3 cells overexpressing retinoic acid receptor (RAR) and retinoid X receptor (RXR). On the other hand, CCAAT/enhancer-binding proteins (C/EBP) induced transcriptional activity of the Npt2b gene. Knockdown of the C/EBP gene and a mutation analysis of the C/EBP responsible element in the Npt2b gene promoter indicated that C/EBP plays a pivotal role in the regulation of Npt2b gene transcriptional activity by ATRA. EMSA revealed that the RAR/RXR complex inhibits binding of C/EBP to Npt2b gene promoter. Together, these results suggest that ATRA may reduce the intestinal Pi uptake by preventing C/EBP activation of the intestinal Npt2b gene.
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巻・号 |
477(4)
|
ページ |
817-831
|
公開日 |
2020-2-28
|
DOI |
10.1042/BCJ20190716
|
PII |
222044
|
PMID |
32016357
|
PMC |
PMC7597408
|
MeSH |
Animals
Antineoplastic Agents / pharmacology
CCAAT-Enhancer-Binding Proteins / genetics
CCAAT-Enhancer-Binding Proteins / metabolism
Gene Expression Regulation / drug effects*
Hypophosphatemia, Familial / metabolism
Hypophosphatemia, Familial / pathology
Hypophosphatemia, Familial / prevention & control
Intestine, Small / drug effects
Intestine, Small / metabolism*
Kidney / drug effects
Kidney / metabolism*
Male
Mice
NIH 3T3 Cells
Promoter Regions, Genetic*
Rats
Rats, Wistar
Receptors, Retinoic Acid / genetics
Receptors, Retinoic Acid / metabolism
Retinoid X Receptors / genetics
Retinoid X Receptors / metabolism
Sodium-Phosphate Cotransporter Proteins, Type IIb / genetics*
Sodium-Phosphate Cotransporter Proteins, Type IIb / metabolism
Transcription, Genetic / drug effects*
Tretinoin / pharmacology*
|
IF |
4.097
|
リソース情報 |
ヒト・動物細胞 |
NIH3T3-3-4(RCB1862) |