{"doi":"10.3390/ijms241914855","title":"OGR1 (GPR68) and TDAG8 (GPR65) Have Antagonistic Effects in Models of Colonic Inflammation","abstract":"<jats:p>G-protein-coupled receptors (GPRs), including pro-inflammatory ovarian cancer GPR1 (OGR1/GPR68) and anti-inflammatory T cell death-associated gene 8 (TDAG8/GPR65), are involved in pH sensing and linked to inflammatory bowel disease (IBD). OGR1 and TDAG8 show opposite effects. To determine which effect is predominant or physiologically more relevant, we deleted both receptors in models of intestinal inflammation. Combined Ogr1 and Tdag8 deficiency was assessed in spontaneous and acute murine colitis models. Disease severity was assessed using clinical scores. Colon samples were analyzed using quantitative polymerase chain reaction (qPCR) and flow cytometry (FACS). In acute colitis, Ogr1-deficient mice showed significantly decreased clinical scores compared with wildtype (WT) mice, while Tdag8-deficient mice and double knockout (KO) mice presented similar scores to WT. In Il-10-spontaneous colitis, Ogr1-deficient mice presented significantly decreased, and Tdag8-deficient mice had increased inflammation. In the Il10−/− × Ogr1−/− × Tdag8−/− triple KO mice, inflammation was significantly decreased compared with Tdag8−/−. Absence of Ogr1 reduced pro-inflammatory cytokines in Tdag8-deficient mice. Tdag8−/− had significantly more IFNγ+ T-lymphocytes and IL-23 T-helper cells in the colon compared with WT. The absence of OGR1 significantly alleviates the intestinal damage mediated by the lack of functional TDAG8. Both OGR1 and TDAG8 represent potential new targets for therapeutic intervention.</jats:p>","journal":"International Journal of Molecular Sciences","year":2023,"id":613265,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1579797,"name":"Moana Busch","orcid":null,"position":1,"is_corresponding":false},{"id":1579798,"name":"Cordelia Schuler","orcid":"0000-0002-2995-8170","position":2,"is_corresponding":false},{"id":836060,"name":"Pedro A. Ruiz","orcid":"0000-0001-7528-1474","position":3,"is_corresponding":false},{"id":1579799,"name":"Federica Foti","orcid":null,"position":4,"is_corresponding":false},{"id":1579800,"name":"Nathalie Weibel","orcid":null,"position":5,"is_corresponding":false},{"id":1579801,"name":"Cheryl de Vallière","orcid":"0000-0002-8519-4451","position":6,"is_corresponding":false},{"id":1374264,"name":"Yasser Morsy","orcid":"0000-0001-8234-1877","position":7,"is_corresponding":false},{"id":568455,"name":"Klaus Seuwen","orcid":"0000-0002-6847-6676","position":8,"is_corresponding":false},{"id":1579804,"name":"Martin Hausmann","orcid":null,"position":9,"is_corresponding":false},{"id":240770,"name":"Gerhard Rogler","orcid":"0000-0002-1733-9188","position":10,"is_corresponding":false},{"id":1579796,"name":"Leonie Perren","orcid":"0009-0003-2913-0685","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"OGR1 (GPR68) and TDAG8 (GPR65) Have Antagonistic Effects in Models of Colonic Inflammation","abstract":"<jats:p>G-protein-coupled receptors (GPRs), including pro-inflammatory ovarian cancer GPR1 (OGR1/GPR68) and anti-inflammatory T cell death-associated gene 8 (TDAG8/GPR65), are involved in pH sensing and linked to inflammatory bowel disease (IBD). OGR1 and TDAG8 show opposite effects. To determine which effect is predominant or physiologically more relevant, we deleted both receptors in models of intestinal inflammation. Combined Ogr1 and Tdag8 deficiency was assessed in spontaneous and acute murine colitis models. Disease severity was assessed using clinical scores. Colon samples were analyzed using quantitative polymerase chain reaction (qPCR) and flow cytometry (FACS). In acute colitis, Ogr1-deficient mice showed significantly decreased clinical scores compared with wildtype (WT) mice, while Tdag8-deficient mice and double knockout (KO) mice presented similar scores to WT. In Il-10-spontaneous colitis, Ogr1-deficient mice presented significantly decreased, and Tdag8-deficient mice had increased inflammation. In the Il10−/− × Ogr1−/− × Tdag8−/− triple KO mice, inflammation was significantly decreased compared with Tdag8−/−. Absence of Ogr1 reduced pro-inflammatory cytokines in Tdag8-deficient mice. Tdag8−/− had significantly more IFNγ+ T-lymphocytes and IL-23 T-helper cells in the colon compared with WT. The absence of OGR1 significantly alleviates the intestinal damage mediated by the lack of functional TDAG8. Both OGR1 and TDAG8 represent potential new targets for therapeutic intervention.</jats:p>","is_dataset_classified":null,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37834303","pmcid":"PMC10573511","openalex_id":"https://openalex.org/W4387310252","authors":[],"funders":[{"funder_name":"Swiss National Science Foundation","grant_id":"310030_172870","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"314730_153380","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"153380","title":"The G-protein coupled pH receptor TDAG8 modulates intestinal inflammation"},{"funder_name":"Swiss National Science Foundation","grant_id":"314730","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"310030","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"172870","title":"The role of pH sensing G-protein coupled receptors for intestinal inflammation and fibrosis"}],"total_grants":6,"fwci":2.5502,"citation_percentile":0.90168873,"influential_citations":0,"citation_trend":[{"year":2024,"count":4},{"year":2025,"count":4},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/24/19/14855/pdf?version=1696314442","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/24/19/14855/pdf?version=1696314442","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/24/19/14855/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms241914855","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37834303","host_type":"repository"},{"url":"https://www.zora.uzh.ch/id/eprint/254253/1/ZORA_254253.pdf","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10573511","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms241914855","host_type":"repository"},{"url":"https://doi.org/10.5167/uzh-254253","host_type":""},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10573511/pdf/ijms-24-14855.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10573511","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10573511?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.5167/uzh-254253","host_type":""},{"url":"http://dx.doi.org/10.3390/ijms241914855","host_type":""},{"url":"https://www.zora.uzh.ch/id/eprint/254253/","host_type":""}],"fields_of_study":["Helicobacter pylori-related gastroenterology studies","Inflammatory Bowel Disease","Drug Transport and Resistance Mechanisms","Animals","Mice","Inflammatory Bowel Diseases","Mice, Knockout","Receptors, G-Protein-Coupled","Disease Models, Animal"],"mesh_terms":["Animals","Disease Models, Animal","Inflammatory Bowel Diseases","Mice, Knockout","Receptors, G-Protein-Coupled","Mice"],"keywords":["Inflammation","Receptor","Interleukin 10","Inflammatory bowel disease","Colitis","Immunology","Biology","Internal medicine","Endocrinology","Medicine","Cytokine","Disease","Ulcerative colitis","Crohn’s Disease","Ogr1/gpr68","Ph-sensing G-protein-coupled Receptors","Tdag8/gpr65","1503 Catalysis","sensing G","1607 Spectroscopy","610 Medicine & health","Article","Receptors, G-Protein-Coupled","Mice","1312 Molecular Biology","1706 Computer Science Applications","Animals","610 Medicine &amp; health","Mice, Knockout","1604 Inorganic Chemistry","pH","Inflammatory Bowel Diseases","coupled receptors","Disease Models, Animal","10219 Clinic for Gastroenterology and Hepatology","1606 Physical and Theoretical Chemistry","protein","1605 Organic Chemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T07:23:41.444438Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}