Vitamin D Receptor and Retinoid X Receptor a Status and Vitamin D Insufficiency in Models of Murine Colitis
نویسندگان
چکیده
The anti-inflammatory actions of vitaminDhave long been recognized and its importance inmodulating colon cancer and colitis development is becoming apparent. The vitamin D receptor (VDR) is downregulated in human ulcerative colitis and colitis-associated cancer (CAC); however, its status in murine models of colitis has yet to be explored. Snail and Snail2, zinc-finger transcription factors regulated by inflammatory pathways and able to transcriptionally silence VDR, are upregulated in human Ulcerative Colitis and are associatedwith localized VDR silencing. To signal, VDRmust heterodimerize with retinoid X receptor a (RXRa). If either VDR or RXRa are compromised, vitamin D cannot regulate inflammatory pathways. RXRa is downregulated in human colorectal cancer, yet its expression in human and murine colitis has yet to be investigated. To explore the importance of vitaminD and VDR inmurine colitis, we used acute and chronic azoxymethane/dextran sulfate sodiummodels ofmurine colitis. VDRwas downregulated early in the onset of colitis, whereas RXRa downregulation only occurred as colitis became chronic and developed into CAC. Receptor downregulationwas associatedwith an early increase in the expression of the inflammatory markers, Snail and Snail2. The acute colitis model induced in combination with a vitamin D–deficient diet resulted in increased morbidity, receptor downregulation, inflammatory marker expression, and Snail and Snail2 upregulation. These experiments show the importance of vitamin D and VDR in modulating murine colitis development. Cancer Prev Res; 6(6); 585–93. 2013 AACR.
منابع مشابه
Vitamin D receptor and retinoid X receptor α status and vitamin D insufficiency in models of murine colitis.
The anti-inflammatory actions of vitamin D have long been recognized and its importance in modulating colon cancer and colitis development is becoming apparent. The vitamin D receptor (VDR) is downregulated in human ulcerative colitis and colitis-associated cancer (CAC); however, its status in murine models of colitis has yet to be explored. Snail and Snail2, zinc-finger transcription factors r...
متن کاملP-112: Vitamin D and Fertility
Background: Vitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence that in addition to sex steroid hormones, the classic regulators of human reproduction, vitamin D also modulates reproductive processes in women and men. Materials and Methods: This is a review article that were identifical by com...
متن کاملThe Vitamin D Receptor (VDR) Gene Polymorphisms Fok1 In Obese Pakistanis– a Preliminary Report
Objective: The role of vitamin D has soared to a pinnacle in recent years with functions affecting 229 human genes linked to cardiovascular, autoimmune, humoral, pulmonary and neurological diseases. Relationship between obesity and vitamin D has not as yet been fully established. The objective of the study was to determine the possible relationship between Vitamin D receptor (VDR) gene polymorp...
متن کاملEvaluation of relationship between BMI with vitamin D receptor gene expression and vitamin D levels of follicular fluid in overweight patients with polycystic ovary syndrome
Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder. The roles of vitamin D in the regulation of metabolic modulations specifically involving insulin action and reproduction processing are introduced. In addition, obesity appears to be closely associated with severity of PCOS. The aim of this study was to evaluate the effect of BMI on vitamin D levels in follicular...
متن کامل