Abstract
Adenosine is a signaling nucleoside that is produced following tissue injury, particularly injury involving ischemia and hypoxia. The production of extracellular adenosine and its subsequent signaling through adenosine receptors plays an important role in orchestrating injury responses in multiple organs. There are four adenosine receptors that are widely distributed on immune, epithelial, endothelial, neuronal,and stromal cells throughout the body. Interestingly, these receptors are subject to altered regulation following injury. Studies in mouse models and human cells and tissues have identified that the production of adenosine and its subsequent signaling through its receptors plays largely beneficial roles in acute disease states, with the exception of brain injury. In contrast, if elevated adenosine levels are sustained beyond the acute injury phase, adenosine responses can become detrimental by activating pathways that promote tissue injury and fibrosis. Understanding when during the course of disease adenosine signaling is beneficial as opposed to detrimental and defining the mechanisms involved will be critical for the advancement of adenosine-based therapies for acute and chronic diseases. The purpose of this review is to discuss key observations that define the beneficial and detrimental aspects of adenosine signaling during acute and chronic disease states with an emphasis on cellular processes, such as inflammatory cell regulation, vascular barrier function, and tissue fibrosis.
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Acknowledgments
We would like to thank Tingting Weng and Kelly Volcik for their assistance in preparing and reviewing this manuscript. We would also like to acknowledge the following grant support: National Institute of Health Grants HL070952 to M.R.B. and DK083559 to Y.X. and American Heart Association Grant 12IRG9150001 to Y.X..
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Karmouty-Quintana, H., Xia, Y. & Blackburn, M.R. Adenosine signaling during acute and chronic disease states. J Mol Med 91, 173–181 (2013). https://doi.org/10.1007/s00109-013-0997-1
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DOI: https://doi.org/10.1007/s00109-013-0997-1