International Joint Research Centre on Purinergic Signalling, School of Acupuncture and Tuina/Health and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
International Joint Research Centre on Purinergic Signalling, School of Acupuncture and Tuina/Health and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China; Rudolf Boehm Institute for Pharmacology and Toxicology, University of Leipzig, 04107, Leipzig, Germany.
Neuropharmacology. 2023 Nov 1;238:109655. doi: 10.1016/j.neuropharm.2023.109655. Epub 2023 Jul 7.
Uridine 5'-diphosphoglucose (UDP-G) as a preferential agonist, but also other UDP-sugars, such as UDP galactose, function as extracellular signaling molecules under conditions of cell injury and apoptosis. Consequently, UDP-G is regarded to function as a damage-associated molecular pattern (DAMP), regulating immune responses. UDP-G promotes neutrophil recruitment, leading to the release of pro-inflammatory chemokines. As a potent endogenous agonist with the highest affinity for the P2Y receptor (R), it accomplishes an exclusive relationship between P2YRs in regulating inflammation via cyclic adenosine monophosphate (cAMP), nod-like receptor protein 3 (NLRP3) inflammasome, mitogen-activated protein kinases (MAPKs), and signal transducer and activator of transcription 1 (STAT1) pathways. In this review, we initially present a brief introduction into the expression and function of P2YRs in combination with UDP-G. Subsequently, we summarize emerging roles of UDP-G/P2YR signaling pathways that modulate inflammatory responses in diverse systems, and discuss the underlying mechanisms of P2YR activation in inflammation-related diseases. Moreover, we also refer to the applications as well as effects of novel agonists/antagonists of P2YRs in inflammatory conditions. In conclusion, due to the role of the P2YR in the immune system and inflammatory pathways, it may represent a novel target for anti-inflammatory therapy.
尿苷 5′-二磷酸葡萄糖（UDP-G）作为一种优先激动剂，但其他 UDP-糖，如 UDP 半乳糖，在细胞损伤和细胞凋亡的情况下作为细胞外信号分子发挥作用。因此，UDP-G 被认为是一种损伤相关分子模式（DAMP），调节免疫反应。UDP-G 促进中性粒细胞的募集，导致促炎趋化因子的释放。作为一种与 P2Y 受体（R）具有最高亲和力的强效内源性激动剂，它通过环腺苷酸（cAMP）、核苷酸结合寡聚结构域样受体蛋白 3（NLRP3）炎性体、丝裂原活化蛋白激酶（MAPK）和信号转导和转录激活因子 1（STAT1）途径，在调节炎症方面实现了 P2YRs 的独特关系。在这篇综述中，我们首先简要介绍了 P2YRs 与 UDP-G 结合的表达和功能。随后，我们总结了 UDP-G/P2YR 信号通路在不同系统中调节炎症反应的新作用，并讨论了 P2YR 在炎症相关疾病中激活的潜在机制。此外，我们还提到了 P2YRs 的新型激动剂/拮抗剂在炎症条件下的应用和效果。总之，由于 P2YR 在免疫系统和炎症途径中的作用，它可能成为抗炎治疗的一个新靶点。
