RRC ID 39128
著者 Taketani Y, Segawa H, Chikamori M, Morita K, Tanaka K, Kido S, Yamamoto H, Iemori Y, Tatsumi S, Tsugawa N, Okano T, Kobayashi T, Miyamoto K, Takeda E.
タイトル Regulation of type II renal Na+-dependent inorganic phosphate transporters by 1,25-dihydroxyvitamin D3. Identification of a vitamin D-responsive element in the human NAPi-3 gene.
ジャーナル J Biol Chem
Abstract Vitamin D is an important regulator of phosphate homeostasis. The effects of vitamin D on the expression of renal Na+-dependent inorganic phosphate (Pi) transporters (types I and II) were investigated. In vitamin D-deficient rats, the amounts of type II Na+-dependent Pi transporter (NaPi-2) protein and mRNA were decreased in the juxtamedullary kidney cortex, but not in the superficial cortex, compared with control rats. The administration of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) to vitamin D-deficient rats increased the initial rate of Pi uptake as well as the amounts of NaPi-2 mRNA and protein in the juxtamedullary cortex. The transcriptional activity of a luciferase reporter plasmid containing the promoter region of the human type II Na+-dependent Pi transporter NaPi-3 gene was increased markedly by 1,25-(OH)2D3 in COS-7 cells expressing the human vitamin D receptor. A deletion and mutation analysis of the NaPi-3 gene promoter identified the vitamin D-responsive element as the sequence 5'-GGGGCAGCAAGGGCA-3' nucleotides -1977 to -1963 relative to the transcription start site. This element bound a heterodimer of the vitamin D receptor and retinoid X receptor, and it enhanced the basal transcriptional activity of the promoter of the herpes simplex virus thymidine kinase gene in an orientation-independent manner. Thus, one mechanism by which vitamin D regulates Pi homeostasis is through the modulation of the expression of type II Na+-dependent Pi transporter genes in the juxtamedullary kidney cortex.
巻・号 273(23)
ページ 14575-81
公開日 1998-6-5
DOI 10.1074/jbc.273.23.14575
PII S0021-9258(19)77506-1
PMID 9603973
MeSH Animals COS Cells Calcitriol / pharmacology* Carrier Proteins / metabolism* DNA-Binding Proteins / analysis Gene Expression Regulation / genetics* Humans Immunohistochemistry Kidney Cortex / physiology* Male Microvilli / drug effects* Nuclear Proteins / analysis Phosphate-Binding Proteins Phosphates / metabolism Promoter Regions, Genetic / genetics RNA, Messenger / metabolism Rats Rats, Wistar Receptors, Calcitriol / metabolism Receptors, Retinoic Acid / metabolism Retinoid X Receptors Transcription Factors / metabolism Vitamin D Deficiency / physiopathology
IF 4.238
引用数 112
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞