한빛사 논문
Abstract
Received 15 August 2008; received in revised form 10 March 2009; accepted 17 March 2009. published online 31 March 2009.
AbstractBackground & Aims:
The intestinal epithelium consists of EphB2-positive proliferative basal cryptic cells and EphrinB1-positive, post-mitotic differentiated cells. We investigated the effects of Notch signaling on formation of the EphB2– EphrinB1 boundary using mouse and tissue culture models.Methods:
We created mice in which Mind bomb-1 (Mib1), an essential E3 ubiquitin ligase that activates Notch ligands, was inactivated specifically in the intestinal epithelia ( Vil-Cre;Mib1 f/f); Notch is therefore inactivated in this tissue. We also studied the effects of different inhibitors on intestinal epithelial cells (IEC-6) that express activated Notch. Tissues and cells were analyzed by immunohistochemical and immunoblot analyses.Results:
The intestinal epithelia of Vil-Cre;Mib1 f/f mice had reduced numbers of EphrinB1-positive cells, compared to controls, but increases in EphB2-positive cells; ?-catenin was activated in these cells. These phenotypes were reversed by expression of a constitutively active form of Notch1. In the intestinal epithelial cell line IEC-6, Notch signaling activated the expression of EphrinB1 in a Hes1-independent manner, but down-regulated the expression of EphB2 through the GSK3?-mediated inhibition of ?-catenin.Conclusions:
Notch signaling regulates formation of the EphB2– EphrinB1 boundary in the mouse intestinal epithelium.1 Department of Biological Sciences, Seoul National University, San 56-1, Silim-dong, Gwanak-gu, Seoul, 151-747, South Korea
2 Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, South Korea
3 Section of Crime Scene Investigation, Criminal Investigation Division, Jeju Provincial Police Agency, Jeju City, Jeju-do, Korea
4 Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea
5 Department of Biology, Chungnam National University, College of Medicine, Daejeon, South Korea
6 Department of Pathology, Cancer Research Institute, Chungnam National University College of Medicine, Daejeon, South Korea
* Room 624, Building 504, Department of Biological Sciences, College of Natural Sciences, Seoul National University, San 56-1, Silim-dong, Gwanak-gu, Seoul, 151-747, South Korea, phone: 82-2-880-2638, fax: 82-2-872-1993
PII: S0016-5085(09)00469-7
doi:10.1053/j.gastro.2009.03.046
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