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.
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)