The role of Gα_q/Gα₁₁ signaling in intestinal epithelial cells

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 Gα_q/Gα₁₁ 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 Gα_q/Gα₁₁ were highly expressed in enterocytes, it seemed that enterocytes were not affected in Int-G_q/G₁₁ double knock-out intestine. Thus, we used an intestinal epithelial cell line to examine the role of signaling through Gα_q/Gα₁₁ in enterocytes and manipulated the expression level of Gα_q and/or Gα₁₁. The proliferation was inhibited in IEC-6 cells that overexpressed Gα_q/Gα₁₁ and enhanced in IEC-6 cells in which Gα_q/Gα₁₁ was downregulated. The expression of T-cell factor 1 was increased according to the overexpression of Gα_q/Gα₁₁. The expression of Notch1 intracellular cytoplasmic domain was decreased by the overexpression of Gα_q/Gα₁₁ and increased by the downregulation of Gα_q/Gα₁₁. The relative mRNA expression of Muc2, a goblet cell marker, was elevated in a Gα_q/Gα₁₁ knock-down experiment. Our findings suggest that Gα_q/Gα₁₁-mediated signaling inhibits proliferation and may support a physiological function, such as absorption or secretion, in terminally differentiated enterocytes.