論文 - 詳細
| RRC ID | 18966 |
|---|---|
| 著者 | Dhawan P, Christakos S. |
| タイトル | Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBP beta, and the Vitamin D receptor in 24(OH)ase transcription. |
| ジャーナル | J Cell Biochem |
| Abstract |
Glucocorticoid-induced bone loss has been proposed to involve direct effects on bone cells as well as alterations in calcium absorption and excretion. Since vitamin D is important for the maintenance of calcium homeostasis, in the present study the effects of glucocorticoids on vitamin D metabolism through the expression of 24(OH)ase, an enzyme involved in the catabolism of 1,25(OH)(2)D(3), were examined. Injection of vitamin D replete mice with dexamethasone (dex) resulted in a significant induction in 24(OH)ase mRNA in kidney, indicating a regulatory effect of glucocorticoids on vitamin D metabolism. Whether glucocorticoids can affect 24(OH)ase transcription is not known. Here we demonstrate for the first time a glucocorticoid receptor (GR) dependent enhancement of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. Dex treatment of GR and vitamin D receptor (VDR) transfected COS-7 cells and dex treatment of osteoblastic cells (in which VDR and GR are present endogenously) potentiated 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. In addition, GR was found to cooperate with C/EBP beta to enhance VDR-mediated 24(OH)ase transcription. Using the rat 24(OH)ase promoter with the C/EBP site mutated, GR-mediated potentiation of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription was inhibited. Immunoprecipitation indicated that that GR can interact with C/EBP beta and ChIP/re-ChIP analysis showed that C/EBP beta and GR bind simultaneously to the 24(OH)ase promoter. These findings indicate a novel mechanism whereby glucocorticoids can alter VDR-mediated 24(OH)ase transcription through functional cooperation between C/EBP beta and GR that results in an enhanced ability of C/EBP beta to cooperate with VDR in the regulation of 24(OH)ase. |
| 巻・号 | 110(6) |
| ページ | 1314-23 |
| 公開日 | 2010-8-15 |
| DOI | 10.1002/jcb.22645 |
| PMID | 20564225 |
| MeSH | 3T3 Cells Animals Binding Sites / genetics Blotting, Northern Blotting, Western CCAAT-Enhancer-Binding Protein-beta / genetics CCAAT-Enhancer-Binding Protein-beta / metabolism COS Cells Cell Line, Tumor Chlorocebus aethiops Dexamethasone / pharmacology Gene Expression Regulation / drug effects* Glucocorticoids / pharmacology* Kidney / drug effects Kidney / metabolism Mice Mutation Promoter Regions, Genetic / drug effects Protein Binding / drug effects Receptors, Calcitriol / genetics Receptors, Calcitriol / metabolism Receptors, Glucocorticoid / genetics Receptors, Glucocorticoid / metabolism Reverse Transcriptase Polymerase Chain Reaction Steroid Hydroxylases / genetics* Steroid Hydroxylases / metabolism Transcription, Genetic / drug effects* Transfection Vitamin D3 24-Hydroxylase |
| IF | 4.237 |
| 引用数 | 33 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 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 | MC3T3-E1(RCB1126) |