| RRC ID |
38202
|
| 著者 |
Ishiguro M, Yamamoto H, Masuda M, Kozai M, Takei Y, Tanaka S, Sato T, Segawa H, Taketani Y, Arai H, Miyamoto K, Takeda E.
|
| タイトル |
Thyroid hormones regulate phosphate homoeostasis through transcriptional control of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene.
|
| ジャーナル |
Biochem J
|
| Abstract |
The type IIa renal sodium-dependent phosphate (Na/Pi) co-transporter Npt2a is implicated in the control of serum phosphate levels. It has been demonstrated previously that renal Npt2a protein and its mRNA expression are both up-regulated by the thyroid hormone T3 (3,3',5-tri-iodothyronine) in rats. However, it has never been established whether the induction was mediated by a direct effect of thyroid hormones on the Npt2a promoter. To address the role of Npt2a in T3-dependent regulation of phosphate homoeostasis and to identify the molecular mechanisms by which thyroid hormones modulate Npt2a gene expression, mice were rendered pharmacologically hypo- and hyper-thyroid. Hypothyroid mice showed low levels of serum phosphate and a marked decrease in renal Npt2a protein abundance. Importantly, we also showed that Npt2a-deficient mice had impaired serum phosphate responsiveness to T3 compared with wild-type mice. Promoter analysis with a luciferase assay revealed that the transcriptional activity of a reporter gene containing the Npt2a promoter and intron 1 was dependent upon TRs (thyroid hormone receptors) and specifically increased by T3 in renal cells. Deletion analysis and EMSAs (electrophoretic mobility-shift assays) determined that there were unique TREs (thyroid-hormone-responsive elements) within intron 1 of the Npt2a gene. These results suggest that Npt2a plays a critical role as a T3-target gene, to control phosphate homoeostasis, and that T3 transcriptionally activates the Npt2a gene via TRs in a renal cell-specific manner.
|
| 巻・号 |
427(1)
|
| ページ |
161-9
|
| 公開日 |
2010-3-15
|
| DOI |
10.1042/BJ20090671
|
| PII |
BJ20090671
|
| PMID |
20088828
|
| MeSH |
Animals
COS Cells
Chlorocebus aethiops
Dogs
Electrophoretic Mobility Shift Assay
Female
Gene Expression Regulation*
HeLa Cells
Homeostasis
Humans
Kidney / cytology
Kidney / metabolism*
Luciferases / metabolism
Male
Mice
Mice, Knockout
Phosphates / metabolism*
Promoter Regions, Genetic
Rats
Receptors, Thyroid Hormone / metabolism
Response Elements
Sodium-Phosphate Cotransporter Proteins, Type IIa / physiology*
Transcription, Genetic / drug effects*
Transcriptional Activation
Triiodothyronine / pharmacology*
|
| IF |
4.097
|
| 引用数 |
16
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
