ArticleBMC gastroenterology2019
The impact of the rs8005161 polymorphism on G protein-coupled receptor GPR65 (TDAG8) pH-associated activation in intestinal inflammation.
Article in BMC gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Unveiling the impact of colonic pH and pH-sensing receptors in blood pressure regulation.Gut microbes · 2026Review
- Loss of proton-sensing TDAG8 increases tumor progression in mouse models of colon cancer.Molecular oncology · 2026Article
- pH sensing and inflammation: linking acidic microenvironments to immune reprogramming.Frontiers in immunology · 2026Review
- Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function.Biomolecules · 2025Review
- Activation of the proton-sensing GPCR, GPR65 on fibroblast-like synoviocytes contributes to inflammatory joint pain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Small-molecule probe for IBD risk variant GPR65 I231L alters cytokine signaling networks through positive allosteric modulation.Science advances · 2024Article
- Role of pH-sensing receptors in colitis.Pflugers Archiv : European journal of physiology · 2024Review
- Article
- pH sensing at the intersection of tissue homeostasis and inflammation.Trends in immunology · 2023Review
- Effect of pH and lipopolysaccharide on tight junction regulators and inflammatory markers in intestinal cells as an experimental model of weaning transition in dairy calves.JDS communications · 2023Article
- The Novel Small Molecule BTB Inhibits Pro-Fibrotic Fibroblast Behavior though Inhibition of RhoA Activity.International journal of molecular sciences · 2022Article
- When inflammation turns sour on T cells.Nature immunology · 2022Article
- IBD-associated G protein-coupled receptor 65 variant compromises signalling and impairs key functions involved in inflammation.Cellular signalling · 2022Article
- pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis.International journal of molecular sciences · 2022Article
- GPR65 (TDAG8) inhibits intestinal inflammation and colitis-associated colorectal cancer development in experimental mouse models.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Intestinal Inflammation and Parkinson's Disease.Aging and disease · 2021Review
- A Novel OGR1 (GPR68) Inhibitor Attenuates Inflammation in Murine Models of Colitis.Inflammatory intestinal diseases · 2021Article
- Proton-Sensing GPCRs in Health and Disease.Cells · 2021Review
- pH and Proton Sensor GPR65 Determine Susceptibility to Atopic Dermatitis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- miRNA-7062-5p Promoting Bone Resorption After Bone Metastasis of Colorectal Cancer Through Inhibiting GPR65.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundTissue inflammation in inflammatory bowel diseases (IBD) is associated with a decrease in local pH. The gene encoding G-protein-coupled receptor 65 (GPR65) has recently been reported to be a genetic risk factor for IBD. In response to extracellular acidification, proton activation of GPR65 stimulates cAMP and Rho signalling pathways. We aimed to analyse the clinical and functional relevance of the GPR65 associated single nucleotide polymorphism (SNP) rs8005161.
methods1138 individuals from a mixed cohort of IBD patients and healthy volunteers were genotyped for SNPs associated with GPR65 (rs8005161, rs3742704) and galactosylceramidase (rs1805078) by Taqman SNP assays. 2300 patients from the Swiss IBD Cohort Study (SIBDC) were genotyped for rs8005161 by mass spectrometry based SNP genotyping. IBD patients from the SIBDC carrying rs8005161 TT, CT, CC and non-IBD controls (CC) were recruited for functional studies. Human CD14+ cells were isolated from blood samples and subjected to an extracellular acidic pH shift, cAMP accumulation and RhoA activation were measured.
resultsIn our mixed cohort, but not in SIBDC patients, the minor variant rs8005161 was significantly associated with UC. In SIBDC patients, we observed a consistent trend in increased disease severity in patients carrying the rs8005161-TT and rs8005161-CT alleles. No significant differences were observed in the pH associated activation of cAMP production between IBD (TT, CT, WT/CC) and non-IBD (WT/CC) genotype carriers upon an acidic extracellular pH shift. However, we observed significantly impaired RhoA activation after an extracellular acidic pH shift in IBD patients, irrespective of the rs8005161 allele.
conclusionsThe T allele of rs8005161 might confer a more severe disease course in IBD patients. Human monocytes from IBD patients showed impaired pH associated RhoA activation upon an acidic pH shift.
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