关键词： A1, adenosine receptor A1 A2A, adenosine receptor A2A A2B, adenosine receptor A2B A3, adenosine receptor A3 AIH, autoimmune hepatitis ALT, alanine aminotransferase APAP, acetaminophen APCP, α,β-methylene ADP Adenosine receptors BDL, bile duct ligation CCl4, carbon tetrachloride CD73, ecto-5ʹ-nucleotidase ConA, concanavalin A DCs, dendritic cells DMN, dimethylnitrosamine Ecto-5ʹ-nucleotidase Ectonucleoside triphosphate diphosphohydrolases 1 HCC, hepatocellular carcinoma HFD, high-fat diet HGF, hepatocyte growth factor HSCs, hepatic stellate cells IFN, interferon IL-, interleukin- IPC, ischaemic preconditioning IR, ischaemia-reperfusion Liver MAPK, mitogen-activating protein kinase MCDD, methionine- and choline-deficient diet MHC, major histocompatibility complex NAFLD, non-alcoholic fatty liver disease NK, natural killer NKT, natural killer T NTPDases, ectonucleoside triphosphate diphosphohydrolases Nucleotide receptors P1, purinergic type 1 P2, purinergic type 2 PBC, primary biliary cholangitis PH, partial hepatectomy PKA, protein kinase A PPADS, pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonate Purinergic signals ROS, reactive oxygen species TAA, thioacetamide TNF, tumour necrosis factor Tregs, regulatory T cells VEGF, vascular endothelial growth factor

来  源：   DOI：10.1016/j.jhepr.2020.100165   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
Extracellular nucleotides, including ATP, are essential regulators of liver function and serve as danger signals that trigger inflammation upon injury. Ectonucleotidases, which are expressed by liver-resident cells and recruited immune cells sequentially hydrolyse nucleotides to adenosine. The nucleotide/nucleoside balance orchestrates liver homeostasis, tissue repair, and functional restoration by regulating the crosstalk between liver-resident cells and recruited immune cells. In this review, we discuss our current knowledge on the role of purinergic signals in liver homeostasis, restriction of inflammation, stimulation of liver regeneration, modulation of fibrogenesis, and regulation of carcinogenesis. Moreover, we discuss potential targeted therapeutic strategies for liver diseases based on purinergic signals involving blockade of nucleotide receptors, enhancement of ectonucleoside triphosphate diphosphohydrolase activity, and activation of adenosine receptors.
摘要：
细胞外核苷酸,包括ATP,是肝功能的重要调节因子，并作为损伤时引发炎症的危险信号。外核苷酸酶,由肝脏常驻细胞和募集的免疫细胞表达的核苷酸顺序水解为腺苷。核苷酸/核苷平衡协调肝脏稳态，组织修复,通过调节肝脏驻留细胞和募集的免疫细胞之间的串扰来恢复功能。在这次审查中,我们讨论了我们目前对嘌呤能信号在肝脏稳态中的作用的知识，限制炎症，刺激肝脏再生，调节纤维发生，和致癌作用的调节。此外，我们讨论了基于嘌呤能信号涉及核苷酸受体阻断的肝脏疾病的潜在靶向治疗策略，增强核苷三磷酸二磷酸水解酶活性，和腺苷受体的激活。
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