Carotti Valentina, Rigalli Juan P, van Asbeck-van der Wijst Jenny, Hoenderop Joost G J
Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, Germany.
Biochem Pharmacol. 2022 Sep;203:115192. doi: 10.1016/j.bcp.2022.115192. Epub 2022 Jul 26.
Purinergic signalling is a receptor-mediated process characterized by the binding of extracellular nucleotides and nucleosides to purinergic receptors, which results in the activation intracellular signalling pathways, and, ultimately, leads to changes in cell physiology. Purinergic signalling has been related to the regulation of important physiological processes (e.g., renal electrolyte reabsorption; platelet aggregation; immune response). In addition, it has been associated with pathophysiological situations such as cancer and inflammation. Extracellular vesicles (EVs) are nanoparticles released by all cells of the organism, which play a key role in cell-cell communication. In this regard, EVs can mediate effects on target cells located at distant locations. Within their cargo, EVs contain molecules with the potential to affect purinergic signalling at the target cells and tissues. Here, we review the studies addressing the regulation of purinergic signalling by EVs based on the cell type or tissue where the regulation takes place. In this regard, EVs are found to play a major role in modulating the extracellular ATP levels and, specially, adenosine. This has a clear impact on, for instance, the inflammatory and immune response against cancer cells. Furthermore, we discuss the data available on the regulation of EV secretion and its cargo by purinergic signalling. Here, a major role of the purinergic receptor P2X7 and again, an impact on processes such as inflammation, immune response and cancer pathogenesis has been established. Finally, we highlight uninvestigated aspects of these two regulatory networks and address their potential as therapeutic targets.
嘌呤能信号传导是一种受体介导的过程，其特征在于细胞外核苷酸和核苷与嘌呤能受体结合，导致细胞内信号通路激活，并最终引起细胞生理变化。嘌呤能信号传导与重要生理过程的调节有关（例如，肾脏电解质重吸收；血小板聚集；免疫反应）。此外，它还与癌症和炎症等病理生理情况相关。细胞外囊泡（EVs）是机体所有细胞释放的纳米颗粒，在细胞间通讯中起关键作用。在这方面，EVs可介导对远处靶细胞的影响。在其内容物中，EVs含有可能影响靶细胞和组织中嘌呤能信号传导的分子。在此，我们基于发生调节的细胞类型或组织，综述了关于EVs对嘌呤能信号传导调节的研究。在这方面，发现EVs在调节细胞外ATP水平，特别是腺苷水平方面起主要作用。这对例如针对癌细胞的炎症和免疫反应有明显影响。此外，我们讨论了关于嘌呤能信号传导对EVs分泌及其内容物调节的现有数据。在此，已确定嘌呤能受体P2X7起主要作用，并且再次对炎症、免疫反应和癌症发病机制等过程产生影响。最后，我们强调了这两个调节网络未被研究的方面，并探讨了它们作为治疗靶点的潜力。
