RRC ID 52275
Author Tsukahara T, Hamouda N, Utsumi D, Matsumoto K, Amagase K, Kato S.
Title G protein-coupled receptor 35 contributes to mucosal repair in mice via migration of colonic epithelial cells.
Journal Pharmacol. Res.
Abstract G protein-coupled receptor 35 (GPR35), a receptor for lysophosphatidic acid, is highly expressed in the gastrointestinal tract. Recently, GPR35 has been implicated in the onset of inflammatory bowel disease (IBD), but its role in physiological and pathological processes in the colon remains undefined. In this study, we investigated the contribution of GPR35-mediated signalling to mucosal repair of colonic epithelium in IBD. GPR35 function was examined in a wound healing model, using young adult mouse colon epithelium (YAMC) cells, and in a dextran sulphate sodium (DSS)-induced mouse model of colitis. Cell proliferation, mRNA expression, extracellular signal-regulated kinase (ERK) activation, and protein localization were determined by MTT assay, quantitative RT-PCR, western blotting, and immunohistochemistry, respectively. GPR35 agonists (YE120, zaprinast, and pamoic acid) promoted wound repair in a concentration-dependent manner independently of cell proliferation, whereas a specific GPR35 antagonist CID2745687, forskolin, and pertussis toxin reversed the YE120-induced effect. YE120 increased the mRNA expression of fibronectin and its receptor integrin α5, and ERK1/2 phosphorylation, but these responses were attenuated by CID2745687 and forskolin. Furthermore, the severity of DSS-induced colitis was significantly reduced by daily injections of pamoic acid via upregulation of fibronectin and integrin α5 in the colonic epithelium. GPR35 signalling promotes mucosal repair by inducing fibronectin and integrin α5 expression, coupling to Gi protein, and activating ERK1/2 in colonic epithelial cells. These findings define GPR35 as a candidate therapeutic target in IBD.
Volume 123
Pages 27-39
Published 2017-9
DOI 10.1016/j.phrs.2017.06.009
PII S1043-6618(17)30282-7
PMID 28648739
MeSH Animals Cell Line Cell Movement / physiology* Colitis / chemically induced Colitis / drug therapy Colitis / metabolism Colitis / pathology Colon / cytology* Colon / metabolism Colon / pathology Cytokines / genetics Dextran Sulfate Epithelial Cells / metabolism Epithelial Cells / physiology* Extracellular Signal-Regulated MAP Kinases / metabolism Fibronectins / metabolism Furans / pharmacology Integrins / metabolism Intestinal Mucosa / metabolism* Male Mice, Inbred C57BL Naphthols / therapeutic use Nitriles / pharmacology Peroxidase / metabolism Purinones / pharmacology RNA, Messenger / metabolism Rats Receptors, G-Protein-Coupled / agonists* Receptors, G-Protein-Coupled / antagonists & inhibitors Receptors, G-Protein-Coupled / metabolism Wound Healing / physiology*
IF 5.574
Human and Animal Cells IEC 6(RCB0993)