Abstract
Extracellular ATP functions as a signaling messenger through its actions on purinergic receptors, and is known to be involved in numerous physiological and pathophysiological processes throughout the body, including in the lungs and airways. Consequently, purinergic receptors are considered to be promising therapeutic targets for many respiratory diseases, including asthma. This review explores how online bioinformatics resources combined with recently generated datasets can be utilized to investigate purinergic receptor gene expression in tissues and cell types of interest in respiratory disease to identify potential therapeutic targets, which can then be investigated further. These approaches show that different purinergic receptors are expressed at different levels in lung tissue, and that purinergic receptors tend to be expressed at higher levels in immune cells and at more moderate levels in airway structural cells. Notably, P2RX1, P2RX4, P2RX7, P2RY1, P2RY11, and P2RY14 were revealed as the most highly expressed purinergic receptors in lung tissue, therefore suggesting that these receptors have good potential as therapeutic targets for asthma and other respiratory diseases.
Highlights
The critical role of intracellular adenosine 5’-triphosphate (ATP) in energy transfer within the cell is well-recognized
While all three compounds have been shown to have antitussive effects, taste disturbance is still experienced with these compounds, albeit to a lesser extent than with gefapixant [69]. Given their ability to alter ion transport, purinergic receptors are considered promising targets for the treatment of cystic fibrosis (CF), where defective ion transport and subsequent abnormal airway surface liquid volume is caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene [2, 3]
We have demonstrated how bioinformatics resources can be utilized to explore purinergic receptor gene expression in tissues and cell types of interest and to identify potential therapeutic targets
Summary
The critical role of intracellular adenosine 5’-triphosphate (ATP) in energy transfer within the cell is well-recognized. Utilized in our previous studies [27], and expression data for individual purinergic receptors in each HASM and HBEC donor can be found in the Supplementary Material The left-hand panel of each UMAP plot in Figure 3 shows gene expression level, with lighter colors indicating higher expression, and the upper and the lower right-hand panels of each plot indicate the disease state and cell type associated with each region of the plot, respectively These figures can both be used to demonstrate that P2RX4 is highly expressed in macrophages and alveolar macrophages, and moderately expressed in several epithelial cell types, suggesting that P2RX4 could be a potential therapeutic target for these cell types. Increased levels of adenosine have been found in bronchoalveolar lavage fluid (BALF)
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