title: AhR activation by 6-formylindolo[3,2-b]carbazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibit the development of mouse intestinal epithelial cells.
abstract: The intestinal epithelium plays a central role in immune homeostasis in the intestine. AhR, a ligand-activated transcription factor, plays an important role in diverse physiological processes. The intestines are exposed to various exogenous and endogenous AhR ligands. Thus, AhR may regulate the intestinal homeostasis, directly acting on the development of intestinal epithelial cells (IEC). In this study, we demonstrated that 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibited the in vitro development of mouse intestinal organoids. The number of Paneth cells in the small intestine and the depth of crypts of the small and large intestines were reduced in mice administrated with FICZ. Immunohistochemical and flow cytometric assays revealed that AhR was highly expressed in Lgr5(+) stem cells. FICZ inhibited Wnt signaling lowering the level of β-catenin protein. Gene expression analyses demonstrated that FICZ increased expression of Lgr5, Math1, BMP4, and Indian Hedgehog while inhibiting that of Lgr4.
authors.affiliation: Department of Biology, Changwon National University, Changwon, Kyungnam, 641-773, Korea. Electronic address: parkjh@changwon.ac.kr.
authors.forename: Joo-Hung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biology, Changwon National University, Changwon, Kyungnam, 641-773, Korea.
authors.forename: Ah-Jeong
authors.initials: AJ
authors.lastname: Choi
authors.affiliation: Department of Biology, Changwon National University, Changwon, Kyungnam, 641-773, Korea.
authors.forename: Soo-Ji
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biology, Changwon National University, Changwon, Kyungnam, 641-773, Korea.
authors.forename: Seon-Woo
authors.initials: SW
authors.lastname: Cheong
authors.affiliation: Department of Biology, Changwon National University, Changwon, Kyungnam, 641-773, Korea.
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Jeong
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D006131:Growth Inhibitors / Q000633:toxicity; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
chemical_list: D002227:Carbazoles; D006131:Growth Inhibitors; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon
keywords: AhR; Crypt; FICZ; Intestinal epithelial cells; Intestinal organoid; Lgr5(+) stem cells