CDX2 increases SLC7A7 expression and proliferation of pig intestinal epithelial cells
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Xiang-guang Li1, Gao-feng Xu1, Zhen-ya Zhai1, Chun-qi Gao1, Hui-chao Yan1, Qian-yun Xi1, Wu-tai Guan1, Song-bo Wang1, Xiu-qi Wang1
1College of Animal Science, South China Agricultural University/National Engineering Research Center for Breeding Swine Industry, Guangzhou 510642, China
Xiu-qi Wang, email: [email protected]
Keywords: CDX2, cell proliferation, intestinal epithelial cells, solute carrier family 7 member 7, pig
Received: January 11, 2016 Accepted: March 31, 2016 Published: April 21, 2016
Nutrient absorption mediated by nutrient transporters expressed in the intestinal epithelium supplies substrates to support intestinal processes, including epithelial cell proliferation. We evaluated the role of Caudal type homeobox 2 (CDX2), an intestine-specific transcription factor, in the proliferation of pig intestinal epithelial cells (IPEC-1) and searched for novel intestinal nutrient transporter genes activated by CDX2. Our cloned pig CDX2 cDNA contains a “homeobox” DNA binding motif, suggesting it is a transcriptional activator. CDX2 overexpression in IPEC-1 cells increased cell proliferation, the percentage of cells in S/G2 phase, and the abundance of transcripts of the cell cycle-related genes Cyclin A2; Cyclin B; Cyclin D2; proliferating cell nuclear antigen; and cell cycle cyclin-dependent kinases 1, 2 and 4, as well as the predicted CDX2 target genes SLC1A1, SLC5A1 and SLC7A7. In addition, luciferase reporter and chromatin immunoprecipitation assays revealed that CDX2 binds directly to the SLC7A7 promoter. This is the first report of CDX2 function in pig intestinal epithelial cells and identifies SLC7A7 as a novel CDX2 target gene. Our findings show that nutrient transporters are activated during CDX2-induced proliferation of normal intestinal epithelial cells.
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