The role of G?q/G?11 signaling in intestinal epithelial cells.

ABSTRACT: Intestinal homeostasis and the coordinated actions of digestion, absorption and excretion are tightly regulated by a number of gastrointestinal hormones. Most of them exert their actions through G-protein-coupled receptors. Recently, we showed that the absence of G?q/G?11 signaling impaired the maturation of Paneth cells, induced their differentiation toward goblet cells, and affected the regeneration of the colonic mucosa in an experimental model of colitis. Although an immunohistochemical study showed that G?q/G?11 were highly expressed in enterocytes, it seemed that enterocytes were not affected in Int-Gq/G11 double knock-out intestine. Thus, we used an intestinal epithelial cell line to examine the role of signaling through G?q/G?11 in enterocytes and manipulated the expression level of G?q and/or G?11. The proliferation was inhibited in IEC-6 cells that overexpressed G?q/G?11 and enhanced in IEC-6 cells in which G?q/G?11 was downregulated. The expression of T-cell factor 1 was increased according to the overexpression of G?q/G?11. The expression of Notch1 intracellular cytoplasmic domain was decreased by the overexpression of G?q/G?11 and increased by the downregulation of G?q/G?11. The relative mRNA expression of Muc2, a goblet cell marker, was elevated in a G?q/G?11 knock-down experiment. Our findings suggest that G?q/G?11-mediated signaling inhibits proliferation and may support a physiological function, such as absorption or secretion, in terminally differentiated enterocytes.

SUBMITTER: Mashima H 

PROVIDER: S-EPMC5789759 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature