Author Interviews, Gastrointestinal Disease, Inflammation / 27.10.2016
pH Sensing Molecules May Play a Role in Initiating Inflammatory Bowel Disorders
MedicalResearch.com Interview with:
Cheryl de Valliere, PhD
University Hospital Zurich
Division of Gastroenterology and Hepatology
Zurich Switzerland
and co-authors
Gerhard Rogler, Jesus Cosin Roger, Pedro A. Ruiz
MedicalResearch.com: What is the background for this study?
Response: Inflammatory Bowel Disease (IBD), including ulcerative colitis and Crohn’s disease, gives rise to chronic relapsing inflammation of the gastrointestinal (GI) tract, resulting in a disruption of the epithelial barrier function and exacerbated innate and adaptive immune responses. One of the most important features under these inflammatory conditions is the presence of hypoxic areas where oxygen levels are lower than in normal tissue. It has been widely reported that the main transcription factor regulating cellular responses to hypoxia, hypoxia inducible factor (HIF)-1, is significantly induced in patients with IBD compared with healthy subjects. Furthermore, hypoxia is not only linked to inflammation, but also influences the local tissue pH, leading to an reduction of the pH in the inflamed mucosa compared with the non-inflamed one.
A family of pH-sensing G-protein coupled receptors (GPCRs), including the receptor T-cell death-associated gene 8 (TDAG8) and the ovarian cancer G-protein coupled receptor 1 (OGR1 or GPR68), play an important role in physiological pH homeostasis. At low extracellular pH, second messenger signaling pathways are activated by protons binding to the histidine residues located on the extracellular region of the receptor. Recent studies have reported a link between IBD and this family of pH-sensing receptors. Indeed, TDAG8 has been identified as an IBD risk gene and we have previously reported an increased expression of OGR1 in patients with IBD compared with healthy subjects.
To better understand the basic mucosal inflammatory mechanisms, and foster the development of new treatment options (e.g. pH receptor blockers and OGR1 antagonists) for chronic mucosal inflammatory diseases, we investigated the effects of hypoxia on pH-sensing OGR1 in the intestinal mucosa and associated cells.
(more…)