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| 维生素D分子机制及其与成纤维生长因子23、Klotho 相关性的新进展 |
| The molecular mechanism of vitamin D and its association with FGF23 and Klotho |
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| DOI：10.3969/j.issn.1006.7108.2014.11.022 |
| 中文关键词: 维生素D 维生素D受体；成纤维生长因子23 ； Klotho |
| 英文关键词:Vitamin D Vitamin D receptor FGF23 Klotho |
| 基金项目:军事医学创新专项（13CXZ029) |
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| 中文摘要: |
| 维生素D( VD)的经典作用为调节钙磷和骨代谢，同时还与免疫系统、细胞增殖和分化等有重要联系。1α，25-羟基维生素D( 1,25 (OH) D)配体结合维生素D受体(VDR)引发VDR与维甲酸X受体(RXR)紧密结合，且配体结合的VDR-RXR异二聚体识别VD调控基因序列中的维生素D应答元件（VDREs)。虽然1,25 ( OH) D-VDR可通过非基因机制快速发挥作用，但1,25( OH) D-VDR主要通过基因机制实现功能。1,25( OH) D-VDR可控制基因转录，VD配体、VDRE的DNA序列以及招募的共激活因子/共阻遏因子都能影响基因表达。1,25( OH) D-VDR调节基因的VDREs具有重要功能。通过推测RANKL基因染色质成环模型表明DNA成环和染色质的结构在VD调节基因表达的作用中发挥主要作用。1,25 ( OH) D-VDR调节基因表达可以延缓衰老和老年性疾病，比如癌症、2型糖尿病和心血管疾病。针对VD在磷酸盐代谢与衰老方面的关系巳有了新的认识，认为1,25( OH) D-VDR诱导的骨骼中FGF23和肾脏中Klotho蛋白在该代谢途径中发挥重要作用，VD调节磷酸盐稳态可能是延缓衰老及相关慢性疾病的机制。 |
| 英文摘要: |
| The classic role of vitamin D (VD) is to regulate metabolism of calcium，phosphorus and the bone. It is also important in the immune system，cell proliferation and differentiation. The liganding of 1,25( OH) D-VDR triggers tight association between VDR and a retinoid X receptor ( RXR). VDR-RXR heterodimer is conformed to recognize vitamin D responsive elements (VDREs) in the DNA sequence of vitamin D-regulated genes. Although the hormone-receptor complex acts rapidly via nongenomic mechanisms，1,25( OH) D-VDR functions mainly through genomic mechanisms. 1，25 (OH) D-VDR regulates gene transcription. The vitamin D ligand，the DNA sequence of the VDRE，and the recruited coactivator/corepressor are all capable of influencing gene expression. VDREs regulated by 1,25 (OH) D-VDR have important function. By using RANKL gene chromatin loop model，it is suggested that DNA-looping and chromatin architecture play a main role in VD regulation of gene expression. Gene expression regulated by 1,25 (OH) D-VDR may delay chronic disorders of aging such as cancer，type 2 diabetes，and cardiovascular diseases. A new knowledge about the association between VD and phosphate metabolism and aging is that 1,25 (OH) D-VDR plays an important role in this metabolic pathway through FGF23 in the bone and Klotho in the kidney. Phosphate stability regulated by VD may be the mechanism of age delaying. |
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