論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MDCK(RCB0995) COS-7(RCB0539) Hep G2 HeLa |