GPR182生物学功能与临床转化应用的研究 进展

Research Progress on the Biological Functions and Clinical Translational Applications of GPR182

摘要: G蛋白偶联受体(G protein-coupled receptor, GPCR)家族是人体中数量最庞大的膜蛋白家族，在调控多种生理病理过程中发挥重要作用，也是重要的药物靶点类别。G蛋白偶联受体182 (G protein-coupled receptor 182, GPR182)作为一种新型非典型趋化因子受体(atypical chemokine receptor, ACKR)，主要表达于血管内皮细胞、肝脏窦状内皮细胞等，通过糖胺聚糖(glycosaminoglycan, GAG)结合基序识别并结合趋化因子，依赖β-arrestin (β-抑制蛋白)和G蛋白偶联受体激酶(g protein-coupled receptor kinase, GRK)的协同作用，参与配体的结合与清除；通过与C-X-C趋化因子受体4 (C-X-C chemokine receptor 4, CXCR4)竞争性结合C-X-C趋化因子配体12 (C-X-C chemokine motif ligand 12, CXCL12)调控CXCL12-CXCR4轴信号传导。生理状态下，GPR182可以在血管生成中发挥负向调控作用，参与胚胎血管发育与造血稳态维持；病理状态下，GPR182在肝细胞癌中的表达水平显著下降，且与患者预后相关。本文重点围绕GPR182的生物学功能及信号传导机制展开详细论述，探讨了GPR182的临床转化前景，为GPR182的相关基础研究和临床转化应用提供精确参考。

Abstract: G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human body, playing crucial roles in regulating a variety of physiological and pathological processes, and are also an important class of drug targets. G protein-coupled receptor 182 (GPR182), a novel atypical chemokine receptor (ACKR), is mainly expressed in vascular endothelial cells, hepatic sinusoidal endothelial cells, etc. It recognizes and binds chemokines through its glycosaminoglycan (GAG)-binding motif, and participates in ligand binding and clearance depending on the synergistic effect of β-arrestin and G protein-coupled receptor kinase (GRK). Additionally, GPR182 regulates the signaling of the C-X-C chemokine motif ligand 12 (CXCL12)-C-X-C chemokine receptor 4 (CXCR4) axis by competitively binding to CXCL12 with CXCR4. Under physiological conditions, GPR182 exerts a negative regulatory role in angiogenesis and is involved in embryonic vascular development and the maintenance of hematopoietic homeostasis. Under pathological conditions, its expression is significantly downregulated in hepatocellular carcinoma (HCC) and is associated with patient prognosis. This review focuses on the detailed discussion of the biological functions and signaling mechanisms of GPR182, explores its clinical translational prospects, and provides an accurate reference for basic research and clinical translational applications related to GPR182.