Role of pH-sensing receptors in colitis.

Autor: Hausmann M; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091, Zurich, CH, Switzerland. martin.hausmann@usz.ch., Seuwen K; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091, Zurich, CH, Switzerland., de Vallière C; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091, Zurich, CH, Switzerland., Busch M; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091, Zurich, CH, Switzerland., Ruiz PA; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091, Zurich, CH, Switzerland., Rogler G; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091, Zurich, CH, Switzerland.
Jazyk: angličtina
Zdroj: Pflugers Archiv : European journal of physiology [Pflugers Arch] 2024 Apr; Vol. 476 (4), pp. 611-622. Date of Electronic Publication: 2024 Mar 22.
DOI: 10.1007/s00424-024-02943-y
Abstrakt: Low pH in the gut is associated with severe inflammation, fibrosis, and colorectal cancer (CRC) and is a hallmark of active inflammatory bowel disease (IBD). Subsequently, pH-sensing mechanisms are of interest for the understanding of IBD pathophysiology. Tissue hypoxia and acidosis-two contributing factors to disease pathophysiology-are linked to IBD, and understanding their interplay is highly relevant for the development of new therapeutic options. One member of the proton-sensing G protein-coupled receptor (GPCR) family, GPR65 (T-cell death-associated gene 8, TDAG8), was identified as a susceptibility gene for IBD in a large genome-wide association study. In response to acidic extracellular pH, GPR65 induces an anti-inflammatory response, whereas the two other proton-sensing receptors, GPR4 and GPR68 (ovarian cancer G protein-coupled receptor 1, OGR1), mediate pro-inflammatory responses. Here, we review the current knowledge on the role of these proton-sensing receptors in IBD and IBD-associated fibrosis and cancer, as well as colitis-associated cancer (CAC). We also describe emerging small molecule modulators of these receptors as therapeutic opportunities for the treatment of IBD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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