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Indole-3-Carbinol Promotes Goblet-Cell Differentiation Regulating Wnt and Notch Signaling Pathways AhR-Dependently
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논문 기본 정보

Type
Academic journal
Author
박주형 (창원대학교) 이정민 (창원대학교) 이은진 (창원대학교) 황원빈 (창원대학교) Da Jeong Kim (창원대학교)
Journal
The Korean Society For Molecular And Cellular Biology Molecules and Cells Molecules and Cells 제41권 제4호 KCI Accredited Journals
Published
2018.3
Pages
290 - 300 (11page)
DOI
10.14348/molcells.2018.2167

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Indole-3-Carbinol Promotes Goblet-Cell Differentiation Regulating Wnt and Notch Signaling Pathways AhR-Dependently
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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.
#AhR #goblet #intestinal organoid #I3C #Notch

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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 Crossref Ahmad, A. / 2010 / Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy / Curr Drug Targets 11:652~666 Crossref Barker, N. / 2007 / Identification of stem cells in small intestine and colon by marker gene Lgr5 / Nature 449:1003~1007 Crossref Barker, N. / 2008 / The intestinal stem cell / Genes Dev. 22:1856~1864 Crossref Barouki, R. / 2007 / The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein / FEBS Lett. 581:3608~3615 Crossref

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