Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis

Journal of Crohn's & Colitis
Senta HutterMartin Hausmann

Abstract

pH-sensing ovarian cancer G-protein coupled receptor-1 [OGR1/GPR68] is regulated by key inflammatory cytokines. Patients suffering from inflammatory bowel diseases [IBDs] express increased mucosal levels of OGR1 compared with non-IBD controls. pH-sensing may be relevant for progression of fibrosis, as extracellular acidification leads to fibroblast activation and extracellular matrix remodelling. We aimed to determine OGR1 expression in fibrotic lesions in the intestine of Crohn's disease [CD] patients, and the effect of Ogr1 deficiency in fibrogenesis. Human fibrotic and non-fibrotic terminal ileum was obtained from CD patients undergoing ileocaecal resection due to stenosis. Gene expression of fibrosis markers and pH-sensing receptors was analysed. For the initiation of fibrosis in vivo, spontaneous colitis by Il10-/-, dextran sodium sulfate [DSS]-induced chronic colitis and the heterotopic intestinal transplantation model were used. Increased expression of fibrosis markers was accompanied by an increase in OGR1 [2.71 ± 0.69 vs 1.18 ± 0.03, p = 0.016] in fibrosis-affected human terminal ileum, compared with the non-fibrotic resection margin. Positive correlation between OGR1 expression and pro-fibrotic cytokines [TGFB1 and CT...Continue Reading

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Citations

Jan 31, 2019·International Journal of Molecular Sciences·Shu Z WileyPaul A Insel
Jun 20, 2019·International Journal of Molecular Sciences·Jong Han LeeHee-Sook Jun
Apr 8, 2020·World Journal of Gastroenterology : WJG·Zhen ZengHu Zhang

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