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CC亚族趋化因子及其受体在慢性肝病中的作用及机制

张子欣 李晖 王佳慧 陶雨静 曾小晏

引用本文:
Citation:

CC亚族趋化因子及其受体在慢性肝病中的作用及机制

DOI: 10.12449/JCH240528
基金项目: 

国家自然科学基金面上项目 (82274323)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:张子欣负责撰写论文;王佳慧,陶雨静,曾小晏参与收集文献,修改论文;李晖负责拟定写作思路,指导文章撰写并最后定稿。
详细信息
    通信作者:

    李晖, 1400124746@qq.com (ORCID: 0000-0002-5919-1396)

Role and mechanism of CC chemokines and their receptors in chronic liver diseases

Research funding: 

General Program of the National Natural Science Foundation of China (82274323)

More Information
    Corresponding author: LI Hui, 1400124746@qq.com (ORCID: 0000-0002-5919-1396)
  • 摘要: 近年来,慢性肝病的发病率持续上升,如慢性乙型肝炎、非酒精性脂肪性肝病、肝纤维化、肝硬化、肝细胞癌等,且发病年龄逐渐呈现低龄化趋势。目前许多CC亚族趋化因子在慢性肝病中的作用得到了证实,本文对近年来影响慢性肝病的CC亚家族趋化因子及其受体的研究进展进行总结,探讨其在慢性肝病中的应用潜力,以期为慢性肝病的防治研究提供新思路。

     

  • 图  1  CC亚族趋化因子及其受体在慢性肝病中的作用机制

    Figure  1.  Mechanism of CC subfamily chemokines and receptors in chronic liver disease

    表  1  CC亚族趋化因子及其受体在慢性肝病中的作用

    Table  1.   Role of CC subfamily chemokines and receptors in chronic liver disease

    趋化因子 趋化因子受体 在慢性肝病中的作用
    CCL1 CCR8 CCR8促进炎性单核细胞向损伤肝脏的迁移,并使其分化为具有促炎表型的巨噬细胞,发挥促纤维化作用
    CCL2 CCR2 CCL2与其受体CCR2结合招募单核-巨噬细胞到损伤的肝脏,抑制CCL2的表达,可减少肝纤维化- HCC动物模型中的Ⅰ型胶原、Ⅳ型胶原和病理性血管生成,从而改善肝脏结构紊乱,高浓度CCL2及其受体可对单核/巨噬细胞积聚、炎症过程启动以及纤维蛋白生成产生影响,并促进癌症的发生
    CCL3/CCL5 CCR1/CCR5 CCL3表达促进了HSC的增殖和迁移、促进巨噬细胞浸润到肝脏,分化为M1表型,CCL3缺乏可减轻小鼠肝纤维化。CCL3可以向HCC募集白细胞,促进HCC的发生。CCL3是NAFLD进展的致病因素。CCL5可通过ROS的产生、Akt/ERK的信号传导,诱导HSC迁移;并在纤维化和伤口愈合过程中,招募CCR5阳性的肝祖细胞。CCR5和CCR1在慢性肝损伤的情况下可以促进肝纤维化。CVC是CCR2/CCR5双重拮抗剂,通过抑制炎症性FSCN1+巨噬细胞和HERC6+中性粒细胞的肝脏积聚来改善细胞外基质沉积和肝纤维化。CCL5为HCC诊断的潜在生物标志物,CCL5的灵敏度和特异度较CCL4更高
    CCL4 CCL4为HCC诊断的潜在生物标志物
    CCL11 CCL11通过刺激Jagged 1的转录以调节HSC的活化,发挥促纤维化的作用
    CCL14 CCL14为肿瘤抑制因子,可用于判断HCC患者的预后
    CCL15 CCL15的高表达与HCC患者的不良预后相关
    CCL16 CCL16通过使HSC失活抑制肝硬化的进展,并可作为肝硬化发生、进展的标志物
    CCL17 CCR4 CCL17可募集Th17细胞、细胞毒性T淋巴细胞到慢性乙型肝炎患者的肝组织中,阻断CCR4可重建T淋巴细胞抗病毒的免疫应答,并限制Treg的免疫抑制功能,有望成为慢性乙型肝炎的潜在治疗靶点
    CCL19 过表达CCL19,可通过增加肝内CD8+T淋巴细胞,快速清除肝内HBV
    CCL20 CCR6 CCL20可招募巨噬细胞和HSC,并通过激活HSC,发挥促炎及促肝纤维化的作用
    CCL25 CCR9 在NASH小鼠巨噬细胞招募和肝纤维化形成中发挥重要作用。CCR9拮抗剂可阻碍肝纤维化、脂肪性肝炎和HCC进展
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  • 收稿日期:  2023-10-19
  • 录用日期:  2023-12-12
  • 出版日期:  2024-05-25
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