维生素D受体变异对下游靶基因转录调控的研究进展

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (8): 941-945.

维生素D受体变异对下游靶基因转录调控的研究进展

李宝群¹, 沈杰², 周宏灏³

¹承德医学院药理教研室, 承德 067000,河北;
²皖南医学院弋矶山医院安徽省药物临床评价中心,芜湖 241001,安徽;
³中南大学临床药理研究所 ,长沙 410078, 湖南

收稿日期:2009-05-20 修回日期:2009-07-12 出版日期:2009-08-26 发布日期:2020-10-30
通讯作者: 周宏灏,男, 教授, 博士生导师, 工程院院士, 研究方向:遗传药理学。Tel:0731-4805380 　 E-mail:hhzhou2003@163.com
作者简介:李宝群, 女, 硕士, 讲师, 研究方向:遗传药理学。Tel:15028538031 　 E-mail:libao 76@163.com
基金资助:
国家自然科学基金(30528026)

Progress in effects of VDR variant mediated transcriptional regulation on its downstream target gene

LI Bao-qun¹, SHEN Jie², ZHOU Hong-hao³

¹Pharmacology Department of Chengde Medical Colledge, Chengde 067000, Hebei, China;
²Yijishan Hospital of Wannan Medical Colledge, Wuhu 241001, Anhui, China;
³Clinical Pharmacology Insistitute of CSU, Changsha 410078, Hunan, China

Received:2009-05-20 Revised:2009-07-12 Online:2009-08-26 Published:2020-10-30

摘要/Abstract

摘要： 维生素 D3 是人体必需的一种维生素, 属于类固醇激素, 在体内的主要活性形式为 1, 25(OH)₂D₃(简称 VD3),在体内具有重要的生物学功用, 其所有作用的实现都是通过维生素 D受体(VDR)来介导的。VDR 与 VD3 结合后, 可以调控下游一系列靶基因的转录 ,发挥其调节钙磷代谢、调控细胞生长分化等作用 ;另外VDR还在药物代谢、转运、以及药物疗效中起关键作用。VD3 的抗肿瘤机制之一也是当今日益受到重视的化学性保护作用:VD3 通过 VDR 诱导了药物代谢酶CYP450,对内外源性物质尤其是一些前致癌物进行代谢分解继而排出体外的能力加强从而起到抗肿瘤的作用;由此VDR基因变异所产生的蛋白数量或质量的改变也就预示了其在临床上将产生深远影响。

关键词: 维生素 D3, 维生素 D受体, 转录调控, 基因变异, 肠道肿瘤

Abstract: 1,25-(OH)₂D₃ is an essential vitamin that belongs to steroid hormone, the principal recognized biological effect of 1,25-(OH)₂D₃, is to main-tain calcium/phosphate ion homeostasis , regulate cell growth or differentiation and prevent rickets osteomala-cia ;through its combined actionson classical endocrine target tissues including intestine, bone , and kidney , liganding of the vitamin D receptor (VDR)with1,25-(OH)₂D₃ mediates the effects of the 1,25-dihydroxyvi-tamin D3 hormone to alter a series of target gene tran-scription of downstream .In addition , VDR may play an important role in drug metabolism , transportation and therapeutic effect .Mounting epidemiological and experimental evidence also implicates 1, 25-(OH)₂D₃ as an epithelialcell anti-cancer and chemopreventative agent .The 1,25-(OH)₂D₃ ligand and several synthet-ic vitamin D analogs are known to possess potent anti-proliferative , prodifferentiation, and/or cell cycle arrest activities in epithelial cells, whereas 1,25-(OH)₂D₃ likely afford some degree of chemoprotection, another mechanism that could contribute to the antitumor activi-ty of 1,25-(OH)₂D₃ in certain cell types is induction of drug-metabolizing enzyme proteins to initiate enzy-matic detoxification of dietary xenobiotics and deleteri-ous endobiotic compounds.This article reviews the function of VDR on transcriptional regulation to drug-metabolizing enzyme and its relationship between gene polymorphisms and some diseases.

Key words: 1,25-dihydroxyvitaminD3, vitamin D receptor, transcriptional regulation, gene polymorphism, colon tumor

中图分类号:

R587

李宝群, 沈杰, 周宏灏. 维生素D受体变异对下游靶基因转录调控的研究进展[J]. 中国临床药理学与治疗学, 2009, 14(8): 941-945.

LI Bao-qun, SHEN Jie, ZHOU Hong-hao. Progress in effects of VDR variant mediated transcriptional regulation on its downstream target gene[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(8): 941-945.

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