LGR5 and BMI1 Increase Pig Intestinal Epithelial Cell Proliferation by Stimulating WNT/β-Catenin Signaling

Abstract

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

Long noncoding RNA SNHG12 induces proliferation, migration, epithelial–mesenchymal transition, and stemness of esophageal squamous cell carcinoma cells via post‐transcriptional regulation of BMI1 and CTNNB1

“…Members of SNHG family, including SNHG12, are supported to promote cancer development via regulating Wnt/b-catenin pathway (Feng et al, 2018;Shao et al, 2019;Song et al, 2019). As previously reported, BMI1 upregulation could activate Wnt pathway (Li et al, 2018a;Yu et al, 2018). Therefore, it is reasonable to suggest that SNHG12 contributed to stemness and EMT in ESCC cells through BMI/ Wnt/b-catenin pathway.…”

Wnt/β‐catenin‐mediated heat exposure inhibits intestinal epithelial cell proliferation and stem cell expansion through endoplasmic reticulum stress

“…Wnt/β‐catenin pathway is required for maintaining the fate control of ISCs and plays an important role in initial villus formation (van der Flier & Clevers, 2009). A previous study has suggested that epithelial cell proliferation is stimulated by Wnt‐dependent mechanisms (X. G. Li et al, 2018; C. M. Li, Yan, Fu, Xu, & Wang, 2014). Besides, Wnt‐1 signaling inhibits apoptosis by activating β‐catenin/TCF‐mediated transcription, and active β‐catenin promotes cell survival by inhibiting Bax (S. Chen et al, 2001; Wang et al, 2009).…”

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

“…WNT/β-catenin/Tcf4 signaling pathway has been implicated in OPCs maturation and differentiation (21,67,70). In general, β-catenin does not accumulate in the cytoplasm under normal physiological condition because an existing complex consisting of AXIN2, APC, PP2A, GSK3, CK1α, could phosphorylate β-catenin (44). Subsequently, p-β-catenin is degraded by proteasome.…”

“…Subsequently, p-β-catenin is degraded by proteasome. When the WNT/β-catenin/Tcf4 signaling pathway is activated, a large amount of β-catenin accumulates in the cytoplasm, and then binds to TCF4 in the nucleus to activate a series of downstream genes (44). Concurrently, AXIN2 expression is decreased which slows down the degradation of β-catenin.…”