pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis.
OGR1 (GPR68) expression and function
fibroblasts
fibrosis
inflammatory bowel disease
pH-sensing GPCR
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
26 Jan 2022
26 Jan 2022
Historique:
received:
13
12
2021
revised:
14
01
2022
accepted:
17
01
2022
entrez:
15
2
2022
pubmed:
16
2
2022
medline:
9
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35163345
pii: ijms23031419
doi: 10.3390/ijms23031419
pmc: PMC8835966
pii:
doi:
Substances chimiques
GPR68 protein, human
0
GPR68 protein, mouse
0
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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