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

Abstract

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

CLC Number:

R587

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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