Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784649561965330432
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
work_keys_str_mv AT devallierecheryl phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT cosinrogerjesus phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT baeblerkatharina phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT schoepflinanja phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT mamieceline phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT molletmichelle phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT schulercordelia phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT bengssusan phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT langsilvia phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT scharlmichael phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT seuwenklaus phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT ruizpedroa phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT hausmannmartin phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis
AT roglergerhard phsensinggproteincoupledreceptorogr1gpr68expressionandactivationincreasesinintestinalinflammationandfibrosis