Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and B-cell-specific\nMoloney murine leukemia virus insertion site 1 (BMI1) are markers of fast-cycling and quiescent\nintestinal stem cells, respectively. To determine the functions of these proteins in large animals,\nwe investigated their effects on the proliferation of intestinal epithelial cells from pigs. Our results\nindicated that LGR5 and BMI1 are highly conserved proteins and that the pig proteins have greater\nhomology with the human proteins than do mouse proteins. Overexpression of either LGR5 or\nBMI1 promoted cell proliferation and WNT/�²-catenin signaling in pig intestinal epithelial cells\n(IPEC-J2). Moreover, the activation of WNT/�²-catenin signaling by recombinant human WNT3A\nprotein increased cell proliferation and LGR5 and BMI1 protein levels. Conversely, inhibition of\nWNT/�²-catenin signaling using XAV939 reduced cell proliferation and LGR5 and BMI1 protein\nlevels. This is the first report that LGR5 and BMI1 can increase proliferation of pig intestinal epithelial\ncells by activating WNT/�²-catenin signaling.
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