School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia.
Departments of Internal Medicine, and Nutrition and Integrative Physiology, and Center on Aging, University of Utah Health Care System, Salt Lake City, UT, USA.
Nat Rev Nephrol. 2020 Sep;16(9):509-524. doi: 10.1038/s41581-020-0304-7. Epub 2020 Jul 8.
ATP and its ultimate degradation product adenosine are potent extracellular signalling molecules that elicit a variety of pathophysiological functions in the kidney through the activation of P2 and P1 purinergic receptors, respectively. Extracellular purines can modulate immune responses, balancing inflammatory processes and immunosuppression; indeed, alterations in extracellular nucleotide and adenosine signalling determine outcomes of inflammation and healing processes. The functional activities of ectonucleotidases such as CD39 and CD73, which hydrolyse pro-inflammatory ATP to generate immunosuppressive adenosine, are therefore pivotal in acute inflammation. Protracted inflammation may result in aberrant adenosinergic signalling, which serves to sustain inflammasome activation and worsen fibrotic reactions. Alterations in the expression of ectonucleotidases on various immune cells, such as regulatory T cells and macrophages, as well as components of the renal vasculature, control purinergic receptor-mediated effects on target tissues within the kidney. The role of CD39 as a rheostat that can have an impact on purinergic signalling in both acute and chronic inflammation is increasingly supported by the literature, as detailed in this Review. Better understanding of these purinergic processes and development of novel drugs targeting these pathways could lead to effective therapies for the management of acute and chronic kidney disease.
三磷酸腺苷（ATP）及其最终降解产物腺苷是有效的细胞外信号分子，通过分别激活 P2 和 P1 嘌呤能受体，在肾脏中引发多种病理生理功能。细胞外嘌呤可以调节免疫反应，平衡炎症过程和免疫抑制；事实上，细胞外核苷酸和腺苷信号的改变决定了炎症和愈合过程的结果。因此，核苷酸酶如 CD39 和 CD73 的功能活性对于急性炎症至关重要，它们可以将促炎的 ATP 水解为具有免疫抑制作用的腺苷。持续的炎症可能导致异常的腺苷能信号，从而维持炎症小体的激活并加重纤维化反应。各种免疫细胞（如调节性 T 细胞和巨噬细胞）以及肾血管成分上的核苷酸酶表达的改变，控制嘌呤能受体对肾脏靶组织的介导效应。正如本综述所述，越来越多的文献支持 CD39 作为变阻器的作用，可对急性和慢性炎症中的嘌呤能信号产生影响。更好地了解这些嘌呤能过程，并开发针对这些途径的新型药物，可能为急性和慢性肾脏病的治疗提供有效的治疗方法。
