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pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis
Local extracellular acidification occurs at sites of inflammation. Proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1, also known as GPR68) responds to decreases in extracellular pH. Our previous studies show a role for OGR1 in the pathogenesis of mucosal inflammation, suggesting a lin...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835966/ https://www.ncbi.nlm.nih.gov/pubmed/35163345 http://dx.doi.org/10.3390/ijms23031419 |
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author | de Vallière, Cheryl Cosin-Roger, Jesus Baebler, Katharina Schoepflin, Anja Mamie, Céline Mollet, Michelle Schuler, Cordelia Bengs, Susan Lang, Silvia Scharl, Michael Seuwen, Klaus Ruiz, Pedro A. Hausmann, Martin Rogler, Gerhard |
author_facet | de Vallière, Cheryl Cosin-Roger, Jesus Baebler, Katharina Schoepflin, Anja Mamie, Céline Mollet, Michelle Schuler, Cordelia Bengs, Susan Lang, Silvia Scharl, Michael Seuwen, Klaus Ruiz, Pedro A. Hausmann, Martin Rogler, Gerhard |
author_sort | de Vallière, Cheryl |
collection | PubMed |
description | Local extracellular acidification occurs at sites of inflammation. Proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1, also known as GPR68) responds to decreases in extracellular pH. Our previous studies show a role for OGR1 in the pathogenesis of mucosal inflammation, suggesting a link between tissue pH and immune responses. Additionally, pH-dependent signalling is associated with the progression of intestinal fibrosis. In this study, we aimed to investigate OGR1 expression and OGR1-mediated signalling in patients with inflammatory bowel disease (IBD). Our results show that OGR1 expression significantly increased in patients with IBD compared to non-IBD patients, as demonstrated by qPCR and immunohistochemistry (IHC). Paired samples from non-inflamed and inflamed intestinal areas of IBD patients showed stronger OGR1 IHC staining in inflamed mucosal segments compared to non-inflamed mucosa. IHC of human surgical samples revealed OGR1 expression in macrophages, granulocytes, endothelial cells, and fibroblasts. OGR1-dependent inositol phosphate (IP) production was significantly increased in CD14+ monocytes from IBD patients compared to healthy subjects. Primary human and murine fibroblasts exhibited OGR1-dependent IP formation, RhoA activation, F-actin, and stress fibre formation upon an acidic pH shift. OGR1 expression and signalling increases with IBD disease activity, suggesting an active role of OGR1 in the pathogenesis of IBD. |
format | Online Article Text |
id | pubmed-8835966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88359662022-02-12 pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis de Vallière, Cheryl Cosin-Roger, Jesus Baebler, Katharina Schoepflin, Anja Mamie, Céline Mollet, Michelle Schuler, Cordelia Bengs, Susan Lang, Silvia Scharl, Michael Seuwen, Klaus Ruiz, Pedro A. Hausmann, Martin Rogler, Gerhard Int J Mol Sci Article Local extracellular acidification occurs at sites of inflammation. Proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1, also known as GPR68) responds to decreases in extracellular pH. Our previous studies show a role for OGR1 in the pathogenesis of mucosal inflammation, suggesting a link between tissue pH and immune responses. Additionally, pH-dependent signalling is associated with the progression of intestinal fibrosis. In this study, we aimed to investigate OGR1 expression and OGR1-mediated signalling in patients with inflammatory bowel disease (IBD). Our results show that OGR1 expression significantly increased in patients with IBD compared to non-IBD patients, as demonstrated by qPCR and immunohistochemistry (IHC). Paired samples from non-inflamed and inflamed intestinal areas of IBD patients showed stronger OGR1 IHC staining in inflamed mucosal segments compared to non-inflamed mucosa. IHC of human surgical samples revealed OGR1 expression in macrophages, granulocytes, endothelial cells, and fibroblasts. OGR1-dependent inositol phosphate (IP) production was significantly increased in CD14+ monocytes from IBD patients compared to healthy subjects. Primary human and murine fibroblasts exhibited OGR1-dependent IP formation, RhoA activation, F-actin, and stress fibre formation upon an acidic pH shift. OGR1 expression and signalling increases with IBD disease activity, suggesting an active role of OGR1 in the pathogenesis of IBD. MDPI 2022-01-26 /pmc/articles/PMC8835966/ /pubmed/35163345 http://dx.doi.org/10.3390/ijms23031419 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article de Vallière, Cheryl Cosin-Roger, Jesus Baebler, Katharina Schoepflin, Anja Mamie, Céline Mollet, Michelle Schuler, Cordelia Bengs, Susan Lang, Silvia Scharl, Michael Seuwen, Klaus Ruiz, Pedro A. Hausmann, Martin Rogler, Gerhard pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis |
title | pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis |
title_full | pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis |
title_fullStr | pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis |
title_full_unstemmed | pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis |
title_short | pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis |
title_sort | ph-sensing g protein-coupled receptor ogr1 (gpr68) expression and activation increases in intestinal inflammation and fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835966/ https://www.ncbi.nlm.nih.gov/pubmed/35163345 http://dx.doi.org/10.3390/ijms23031419 |
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