The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis.

Autor: Caratis F; Brain Diseases Centre, Medical University of Gdansk, Gdansk, Poland.; Department of Anatomy and Neurobiology, Medical University of Gdansk, Gdansk, Poland., Opiełka M; Brain Diseases Centre, Medical University of Gdansk, Gdansk, Poland., Hausmann M; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Velasco-Estevez M; H12O-CNIO Hematological Malignancies Group, Clinical Research Unit, Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain., Rojek B; Department of Adult Neurology, Medical University of Gdansk & University Clinical Centre, Gdansk, Poland., de Vallière C; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Seuwen K; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Rogler G; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Karaszewski B; Brain Diseases Centre, Medical University of Gdansk, Gdansk, Poland.; Department of Adult Neurology, Medical University of Gdansk & University Clinical Centre, Gdansk, Poland., Rutkowska A; Brain Diseases Centre, Medical University of Gdansk, Gdansk, Poland.; Department of Anatomy and Neurobiology, Medical University of Gdansk, Gdansk, Poland.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Mar 25; Vol. 19 (3), pp. e0283060. Date of Electronic Publication: 2024 Mar 25 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0283060
Abstrakt: Acidosis is one of the hallmarks of demyelinating central nervous system (CNS) lesions in multiple sclerosis (MS). The response to acidic pH is primarily mediated by a family of G protein-coupled proton-sensing receptors: OGR1, GPR4 and TDAG8. These receptors are inactive at alkaline pH, reaching maximal activation at acidic pH. Genome-wide association studies have identified a locus within the TDAG8 gene associated with several autoimmune diseases, including MS. Accordingly, we here found that expression of TDAG8, as opposed to GPR4 or OGR1, is upregulated in MS plaques. This led us to investigate the expression of TDAG8 in oligodendrocytes using mouse and human in vitro and in vivo models. We observed significant upregulation of TDAG8 in human MO3.13 oligodendrocytes during maturation and in response to acidic conditions. However, its deficiency did not impact normal myelination in the mouse CNS, and its expression remained unaltered under demyelinating conditions in mouse organotypic cerebellar slices. Notably, our data revealed no expression of TDAG8 in primary mouse oligodendrocyte progenitor cells (OPCs), in contrast to its expression in primary human OPCs. Our investigations have revealed substantial species differences in the expression of proton-sensing receptors in oligodendrocytes, highlighting the limitations of the employed experimental models in fully elucidating the role of TDAG8 in myelination and oligodendrocyte biology. Consequently, the study does not furnish robust evidence for the role of TDAG8 in such processes. Nonetheless, our findings tentatively point towards a potential association between TDAG8 and myelination processes in humans, hinting at a potential link between TDAG8 and the pathophysiology of MS and warrants further research.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Caratis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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