CDX2 Stimulates the Proliferation of Porcine Intestinal Epithelial Cells by Activating the mTORC1 and Wnt/β-Catenin Signaling Pathways.
CDX2 Stimulates the Proliferation of Porcine Intestinal Epithelial Cells by Activating the mTORC1 and Wnt/β-Catenin Signaling Pathways.
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CDX2 通过激活 mTORC1 和 Wnt/-Catenin 信号通路刺激猪肠上皮细胞增殖
DOI：
10.3390/ijms18112447
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发表时间：
2017-11-18
影响因子：
5.6
通讯作者：
Wang XQ
中科院分区：
文献类型：
--
作者：
Fan HB;Zhai ZY;Li XG;Gao CQ;Yan HC;Chen ZS;Wang XQ
尾型同源异型盒2(CDX2)表达于肠上皮细胞，通过调节细胞增殖，在肠道发育和动态平衡中发挥作用。然而，CDX2是否与哺乳动物靶点雷帕霉素复合体1(MTORC1)和Wnt/β-catenin信号通路协同刺激细胞增殖尚不清楚。本研究旨在探讨CDX2对猪空肠上皮细胞(IPECJ2)增殖的影响及其与mTORC1Wnt/β-catenin信号转导通路的关系。建立CDX2过表达和基因敲除细胞培养模型，探讨CDX2在这两条途径上的调控作用。使用通路特异性拮抗剂来验证其作用。结果表明，CDX2过表达可促进IPEC-J2细胞的增殖，并激活mTORC1和Wnt/β-catenin途径，而CDX2基因敲除则抑制这两条途径。此外，mTORc1和Wnt/(3，5，7，8-tetrahydro-2-[4-(trifluoromethyl)]-4H-catenin途径特异性拮抗剂雷帕霉素和XAV939都能抑制高表达β的细胞的增殖，且雷帕霉素和XAV939具有相加作用。无论用雷帕霉素或XAV939单独或联合处理细胞，mTORC1和Wnt/β-catenin通路均下调，并伴有CDX2表达下降。综上所述，我们的数据表明，CDX2通过激活mTORC1和Wnt/β-catenin信号通路来刺激猪肠道上皮细胞的增殖。
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.
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