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外泌体在肝纤维化发生发展及诊治中的作用

罗业浩 陈秋霞 吕挺 区佩琪 曹知勇 段雪琳

引用本文:
Citation:

外泌体在肝纤维化发生发展及诊治中的作用

DOI: 10.3969/j.issn.1001-5256.2021.12.038
基金项目: 

校级一流学科建设开放课题项目 (2019XK040)

详细信息
    通信作者:

    段雪琳,duanxuelin@126.com

  • 中图分类号: R575.2

Role of exosomes in the development, progression, diagnosis, and treatment of liver fibrosis

Research funding: 

University-Level First-Class Discipline Construction Open Subject Project (2019XK040)

  • 摘要: 越来越多研究证实外泌体与肝纤维化的关系十分密切,外泌体参与细胞因子分泌、巨噬细胞活化、细胞外基质重塑及肝星状细胞活化从而介导肝纤维化的进程。总结了肝纤维化的逆转通过减少外泌体参与的促炎和纤维化细胞因子,减少细胞外基质蛋白的产生,增加胶原酶的活性,最后导致活化的肌成纤维细胞消失。认为外泌体在治疗肝纤维化中具有重要价值,是潜在的诊断和治疗的标志物,在日后的研究中,可以提高外泌体的提取技术及治疗定量的标准化制定。

     

  • 图  1  外泌体的形成过程

    注:外泌体的形成首先经过细胞内吞产生早期核内体,经过膜结合信号蛋白及胞浆蛋白使囊膜内陷,再突入变成胞内多泡体,胞内多泡体与溶酶体及质膜融合,最后将小囊泡排出细胞外形成外泌体。

    图  2  外泌体对肝纤维化的影响机制

    注:富含PDGF、CCN2、TGFβ、CTGF等因子的外泌体促进HSC活化,进一步导致肌成纤维细胞的形成;HSC释放富含外泌体的Twist1和miR214/199-5a簇,以及炎症因子TNFα、IL-1α、IL-β、IL-22和IL-6以使HSC失活;富含MT1-MMP、乙酰肝素酶、整合素、DDR和LOXL2的外泌体参与ECM重塑;富含PDGF、TRAIL、TGFβ1、CD40L等促纤维化介质促进巨噬细胞的活化;外泌体所含的抑制性因子TGFβ、IL-10、甘露糖受体参与巨噬细胞灭活从而诱导肌成纤维细胞凋亡。

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  • 收稿日期:  2021-04-26
  • 录用日期:  2021-06-13
  • 出版日期:  2021-12-20
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