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Vitamin D receptor and retinoid X receptor α status and vitamin D insufficiency in models of murine colitis.

Publication ,  Journal Article
Knackstedt, RW; Moseley, VR; Sun, S; Wargovich, MJ
Published in: Cancer Prev Res (Phila)
June 2013

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 regulated by inflammatory pathways and able to transcriptionally silence VDR, are upregulated in human Ulcerative Colitis and are associated with localized VDR silencing. To signal, VDR must heterodimerize with retinoid X receptor α (RXRα). If either VDR or RXRα are compromised, vitamin D cannot regulate inflammatory pathways. RXRα is downregulated in human colorectal cancer, yet its expression in human and murine colitis has yet to be investigated. To explore the importance of vitamin D and VDR in murine colitis, we used acute and chronic azoxymethane/dextran sulfate sodium models of murine colitis. VDR was downregulated early in the onset of colitis, whereas RXRα downregulation only occurred as colitis became chronic and developed into CAC. Receptor downregulation was associated with 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.

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Published In

Cancer Prev Res (Phila)

DOI

EISSN

1940-6215

Publication Date

June 2013

Volume

6

Issue

6

Start / End Page

585 / 593

Location

United States

Related Subject Headings

  • Vitamin D Deficiency
  • Transcription Factors
  • Snail Family Transcription Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Retinoid X Receptor alpha
  • Receptors, Calcitriol
  • Real-Time Polymerase Chain Reaction
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
 

Citation

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Knackstedt, R. W., Moseley, V. R., Sun, S., & Wargovich, M. J. (2013). Vitamin D receptor and retinoid X receptor α status and vitamin D insufficiency in models of murine colitis. Cancer Prev Res (Phila), 6(6), 585–593. https://doi.org/10.1158/1940-6207.CAPR-12-0488
Knackstedt, Rebecca W., Vondina R. Moseley, Shaoli Sun, and Michael J. Wargovich. “Vitamin D receptor and retinoid X receptor α status and vitamin D insufficiency in models of murine colitis.Cancer Prev Res (Phila) 6, no. 6 (June 2013): 585–93. https://doi.org/10.1158/1940-6207.CAPR-12-0488.
Knackstedt RW, Moseley VR, Sun S, Wargovich MJ. Vitamin D receptor and retinoid X receptor α status and vitamin D insufficiency in models of murine colitis. Cancer Prev Res (Phila). 2013 Jun;6(6):585–93.
Knackstedt, Rebecca W., et al. “Vitamin D receptor and retinoid X receptor α status and vitamin D insufficiency in models of murine colitis.Cancer Prev Res (Phila), vol. 6, no. 6, June 2013, pp. 585–93. Pubmed, doi:10.1158/1940-6207.CAPR-12-0488.
Knackstedt RW, Moseley VR, Sun S, Wargovich MJ. Vitamin D receptor and retinoid X receptor α status and vitamin D insufficiency in models of murine colitis. Cancer Prev Res (Phila). 2013 Jun;6(6):585–593.

Published In

Cancer Prev Res (Phila)

DOI

EISSN

1940-6215

Publication Date

June 2013

Volume

6

Issue

6

Start / End Page

585 / 593

Location

United States

Related Subject Headings

  • Vitamin D Deficiency
  • Transcription Factors
  • Snail Family Transcription Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Retinoid X Receptor alpha
  • Receptors, Calcitriol
  • Real-Time Polymerase Chain Reaction
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL