Opiełka, M. | bioRxiv Science

bioRxiv2024

Expression Profile of Human Bitter Taste Receptors in Human Aortic and Coronary Artery Endothelial Cells

Human bitter taste receptors (TAS2Rs) are G protein-coupled receptors primarily associated with bitter taste perception, in the oral cavity. Many dietary compounds and drugs function as TAS2Rs agonists, activating their intracellular signaling pathways. Emerging evidence indicates TAS2Rs expression in extraoral tissues, including the cardiovascular system, where their functional role remains underexplored.. This study investigates TAS2Rs expression in primary human aortic and coronary artery endothelial cells. Using digital PCR (dPCR), we confirmed the mRNA expression of all 25 TAS2R subtypes in both cell lines. The expression levels were substantially higher in human coronary artery endothelial cells compared to human aortic endothelial cells. We confirmed the protein expression of TAS2R10 and TAS2R38 proteins using Western blot. These findings mark the first identification of TAS2Rs in these endothelial cells, suggesting a potential role in vascular physiology. These findings suggest a potential role for TAS2Rs in vascular physiology, prompting further research into their impact on endothelial function in cardiovascular health and pathology.

cell biology↗

bioRxiv2023

The proton-activated receptor TDAG8 is upregulated in oligodendrocytes during maturation and under acidic conditions.

Acidosis is one of the hallmarks of demyelinating central nervous system (CNS) lesions in multiple sclerosis (MS). 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, while at acidic pH they are maximally activated. Genome-wide association studies identified a locus within the TDAG8 gene to be associated with several autoimmune diseases including MS. Notably, we here found that TDAG8 expression is upregulated in MS plaques which prompted us to explore the expression and function of TDAG8 in the CNS in human MO3.13 oligodendrocytes in vitro and in vivo in the lipopolysaccharide-induced neuroinflammation model. We found that TDAG8 is upregulated in maturing oligodendrocytes and temporarily under acidic conditions. Acidic pH also induces oligodendrocyte branching, inhibits chemotaxis and affects the expression of oligodendrocyte maturation markers, PDGFR and MBP in vitro. Even though myelination was not affected in the adult TDAG8-deficient mice, the expression of human and murine TDAG8 was strongly regulated upon inflammation in vivo in the brain and in vitro in lipopolysaccharide and pro-inflammatory cytokine-treated oligodendrocytes. Together these findings point toward a potential role of TDAG8 in oligodendrocyte biology, neuroinflammation and pathophysiology of MS and provide new directions for further scientific enquiry.

neuroscience↗