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Int. J. Mol. Sci. 2017, 18(11), 2447; https://doi.org/10.3390/ijms18112447

CDX2 Stimulates the Proliferation of Porcine Intestinal Epithelial Cells by Activating the mTORC1 and Wnt/β-Catenin Signaling Pathways

1
College of Animal Science/Guangdong Provincial Key Laboratory of Animal Nutrition Regulation/National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, China
2
Department of Pharmaceutical Science, College of Pharmacy and Health Science, St. John’s University, Queens, NY 11439, USA
*
Author to whom correspondence should be addressed.
Received: 19 October 2017 / Revised: 6 November 2017 / Accepted: 16 November 2017 / Published: 18 November 2017
(This article belongs to the Special Issue Cell Growth Regulation)
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Abstract

Caudal type homeobox 2 (CDX2) is expressed in intestinal epithelial cells and plays a role in gut development and homeostasis by regulating cell proliferation. However, whether CDX2 cooperates with the mammalian target of rapamycin complex 1 (mTORC1) and Wnt/β-catenin signaling pathways to stimulate cell proliferation remains unknown. The objective of this study was to investigate the effect of CDX2 on the proliferation of porcine jejunum epithelial cells (IPEC-J2) and the correlation between CDX2, the mTORC1 and Wnt/β-catenin signaling pathways. CDX2 overexpression and knockdown cell culture models were established to explore the regulation of CDX2 on both pathways. Pathway-specific antagonists were used to verify the effects. The results showed that CDX2 overexpression increased IPEC-J2 cell proliferation and activated both the mTORC1 and Wnt/β-catenin pathways, and that CDX2 knockdown decreased cell proliferation and inhibited both pathways. Furthermore, the mTORC1 and Wnt/β-catenin pathway-specific antagonist rapamycin and XAV939 (3,5,7,8-tetrahydro-2-[4-(trifluoromethyl)]-4H –thiopyrano[4,3-d]pyrimidin-4-one) both suppressed the proliferation of IPEC-J2 cells overexpressing CDX2, and that the combination of rapamycin and XAV939 had an additive effect. Regardless of whether the cells were treated with rapamycin or XAV939 alone or in combination, both mTORC1 and Wnt/β-catenin pathways were down-regulated, accompanied by a decrease in CDX2 expression. Taken together, our data indicate that CDX2 stimulates porcine intestinal epithelial cell proliferation by activating the mTORC1 and Wnt/β-catenin signaling pathways. View Full-Text
Keywords: caudal type homeobox; signaling pathway; cooperation; proliferation caudal type homeobox; signaling pathway; cooperation; proliferation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Fan, H.-B.; Zhai, Z.-Y.; Li, X.-G.; Gao, C.-Q.; Yan, H.-C.; Chen, Z.-S.; Wang, X.-Q. CDX2 Stimulates the Proliferation of Porcine Intestinal Epithelial Cells by Activating the mTORC1 and Wnt/β-Catenin Signaling Pathways. Int. J. Mol. Sci. 2017, 18, 2447.

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