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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

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The role of Gαq/Gα11 signaling in intestinal epithelial cells.

Mashima Hirosato H Watanabe Noboru N Sekine Masanari M Matsumoto Satohiro S Asano Takeharu T Yuhashi Kazuhito K Sagihara Noriyoshi N Urayoshi Shunsuke S Uehara Takeshi T Fujiwara Junichi J Ishii Takehiro T Tsuboi Rumiko R Miyatani Hiroyuki H Ohnishi Hirohide H

Biochemistry and biophysics reports 20180128

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 Gαq/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 im ...[more]

PMID: 29387814

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Project description:Background & aimsProliferation, differentiation, and morphogenesis of the intestinal epithelium are tightly regulated by a number of molecular pathways. Coordinated action of intestine is achieved by gastrointestinal hormones, most of which exert these actions through G-protein-coupled receptors. We herein investigated the role of Gαq/11-mediated signaling in intestinal homeostasis.MethodsIntestinal tissues from control (Gnaqflox/floxGna11+/+ ), Int-Gq knock-out (KO) (VilCre+/-Gnaqflox/floxGna11+/+ ), G11 KO (Gnaqflox/floxGna11-/- ), and Int-Gq/G11 double knock-out (DKO) (VilCre+/-Gnaqflox/floxGna11-/- ) mice were examined by microscopy, transmission electron microscopy, and immunohistochemistry. The effect of Gαq/11-mediated signaling was studied in the cell lineage, proliferation, and apoptosis. Dextran sodium sulfate (DSS) colitis was induced to study the role of Gαq/11 in colon.ResultsPaneth cells were enlarged, increased in number, and mislocalized in Int-Gq/G11 DKO small intestine. Paneth cells also reacted with PAS and Muc2 antibody, indicating an intermediate character of Paneth and goblet cells. The nuclear β-catenin, T-cell factor 1, and Sox9 expression were reduced severely in the crypt base of Int-Gq/G11 DKO intestine. Proliferation was activated in the crypt base and apoptosis was enhanced along the crypt. Int-Gq/G11 DKO mice were susceptible to DSS colitis. Proliferation was inhibited in the crypt of unaffected and regenerative areas. Cystic crypts, periodic acid-Schiff-positive cells, and Muc2-positive cells were unusually observed in the ulcerative region.ConclusionsThe Gαq/11-mediated pathway plays a pivotal role in the preservation of intestinal homeostasis, especially in Paneth cell maturation and positioning. Wnt/β-catenin signaling was reduced significantly in the crypt base in Gαq/G11-deficient mice, resulting in the defective maturation of Paneth cells, induction of differentiation toward goblet cells, and susceptibility to DSS colitis.

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

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The role of Gα<sub>q</sub>/Gα<sub>11</sub> signaling in intestinal epithelial cells.

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Dataset Information

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

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The role of Gα&lt;sub&gt;q&lt;/sub&gt;/Gα&lt;sub&gt;11&lt;/sub&gt; signaling in intestinal epithelial cells.

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OmicsDI is part of the ELIXIR infrastructure

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The role of Gα<sub>q</sub>/Gα<sub>11</sub> signaling in intestinal epithelial cells.