| RRC ID |
39128
|
| Author |
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.
|
| Title |
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.
|
| Journal |
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.
|
| Volume |
273(23)
|
| Pages |
14575-81
|
| Published |
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
|
| Times Cited |
112
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
|
