Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.
The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, School of Pharmacy, Institute for Liver Disease, Anhui Medical University, Hefei, Anhui, China.
J Cell Physiol. 2021 Feb;236(2):851-862. doi: 10.1002/jcp.29932. Epub 2020 Jul 10.
Extracellular adenosine triphosphate (ATP) is a danger signal released by dying and damaged cells, and it functions as an immunostimulatory signal that promotes inflammation. The ectonucleotidases CD39/ectonucleoside triphosphate diphosphohydrolase-1 and CD73/ecto-5'-nucleotidase are cell-surface enzymes that breakdown extracellular ATP into adenosine. This drives a shift from an ATP-driven proinflammatory environment to an anti-inflammatory milieu induced by adenosine. The CD39-CD73-adenosine pathway changes dynamically with the pathophysiological context in which it is embedded. Accumulating evidence suggests that CD39 and CD73 play important roles in liver disease as critical components of the extracellular adenosinergic pathway. Recent studies have shown that the modification of the CD39-CD73-adenosine pathway alters the liver's response to injury. Moreover, adenosine exerts different effects on the pathophysiology of the liver through different receptors. In this review, we aim to describe the role of the CD39-CD73-adenosine pathway and adenosine receptors in liver disease, highlighting potential therapeutic targets in this pathway, which will facilitate the development of therapeutic strategies for the treatment of liver disease.
细胞外三磷酸腺苷 (ATP) 是垂死和受损细胞释放的危险信号，它作为一种免疫刺激信号，促进炎症。细胞表面酶 CD39/核苷酸三磷酸二磷酸水解酶-1 和 CD73/外核苷酸 5′-磷酸酶将细胞外 ATP 分解为腺苷。这促使从由 ATP 驱动的促炎环境转变为由腺苷诱导的抗炎环境。CD39-CD73-腺苷途径随着其所处的病理生理环境而动态变化。越来越多的证据表明，CD39 和 CD73 作为细胞外腺苷能途径的关键组成部分，在肝病中发挥重要作用。最近的研究表明，CD39-CD73-腺苷途径的修饰改变了肝脏对损伤的反应。此外，腺苷通过不同的受体对肝脏的病理生理学产生不同的影响。在这篇综述中，我们旨在描述 CD39-CD73-腺苷途径和腺苷受体在肝病中的作用，强调该途径中的潜在治疗靶点，这将有助于开发治疗肝病的治疗策略。
