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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.3
- 수록면
- 290 - 300 (11page)
- DOI
- 10.14348/molcells.2018.2167
이용수
초록· 키워드
오류제보하기
Using an in vitro model of intestinal organoids derived from intestinal crypts, we examined effects of indole-3-carbinol (I3C), a phytochemical that has anticancer and aryl hydrocarbon receptor (AhR)-activating abilities and thus is sold as a dietary supplement, on the development of intestinal organoids and investigated the underlying mechanisms. I3C inhibited the in vitro development of mouse intestinal organoids. Addition of α-naphthoflavone, an AhR antagonist or AhR siRNA transfection, suppressed I3C function, suggesting that I3C-mediated interference with organoid development is AhR-dependent. I3C increased the expression of Muc2 and lysozyme, lineage-specific genes for goblet cells and Paneth cells, respectively, but inhibits the expression of IAP, a marker gene for enterocytes. In the intestines of mice treated with I3C, the number of goblet cells was reduced, but the number of Paneth cells and the depth and length of crypts and villi were not changed. I3C increased the level of active nonphosphorylated β-catenin, but suppressed the Notch signal. As a result, expression of Hes1, a Notch target gene and a transcriptional repressor that plays a key role in enterocyte differentiation, was reduced, whereas expression of Math1, involved in the differentiation of secretory lineages, was increased. These results provide direct evidence for the role of AhR in the regulation of the development of intestinal stem cells and indicate that such regulation is likely mediated by regulation of Wnt and Notch signals.
목차
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참고문헌 (54)
참고문헌 신청
Abbott, B.D. / 1995 / Developmental expression of two members of a new class of transcription factors: I. Expression of aryl hydrocarbon receptor in the C57BL/6N mouse embryo / Dev. Dyn. 204:133~143
Ahmad, A. / 2010 / Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy / Curr Drug Targets 11:652~666
Barker, N. / 2007 / Identification of stem cells in small intestine and colon by marker gene Lgr5 / Nature 449:1003~1007
Barker, N. / 2008 / The intestinal stem cell / Genes Dev. 22:1856~1864
Barouki, R. / 2007 / The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein / FEBS Lett. 581:3608~3615
Ahmad, A. / 2010 / Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy / Curr Drug Targets 11:652~666
Barker, N. / 2007 / Identification of stem cells in small intestine and colon by marker gene Lgr5 / Nature 449:1003~1007
Barker, N. / 2008 / The intestinal stem cell / Genes Dev. 22:1856~1864
Barouki, R. / 2007 / The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein / FEBS Lett. 581:3608~3615
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