Requirement of G?q/G?11 Signaling in the Preservation of Mouse Intestinal Epithelial Homeostasis.
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ABSTRACT: Proliferation, 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 G?q/11-mediated signaling in intestinal homeostasis.Intestinal 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 G?q/11-mediated signaling was studied in the cell lineage, proliferation, and apoptosis. Dextran sodium sulfate (DSS) colitis was induced to study the role of G?q/11 in colon.Paneth 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 ?-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.The G?q/11-mediated pathway plays a pivotal role in the preservation of intestinal homeostasis, especially in Paneth cell maturation and positioning. Wnt/?-catenin signaling was reduced significantly in the crypt base in G?q/G11-deficient mice, resulting in the defective maturation of Paneth cells, induction of differentiation toward goblet cells, and susceptibility to DSS colitis.
SUBMITTER: Watanabe N
PROVIDER: S-EPMC5247319 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
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