Exosome Uptake through Clathrin-mediated Endocytosis and Macropinocytosis and Mediating miR-21 Delivery
Exosome Uptake through Clathrin-mediated Endocytosis and Macropinocytosis and Mediating miR-21 Delivery
复制标题
通过网格蛋白介导的内吞作用和巨胞饮作用摄取外泌体并介导 miR-21 递送
DOI：
10.1074/jbc.m114.588046
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发表时间：
2014-08-08
影响因子：
4.8
通讯作者：
Xiao, Zhong-Dang
中科院分区：
文献类型：
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作者：
Tian, Tian;Zhu, Yan-Liang;Xiao, Zhong-Dang
外泌体是从许多类型的细胞分泌的纳米级膜囊泡。外泌体携带功能分子，在细胞间传递信息，介导许多生理和病理过程。在本报告中，利用选择性抑制剂，分子工具和特异性内吞标记物，通过高通量显微镜对PC 12细胞来源的外泌体的细胞摄取进行成像并进行统计分析。结果发现，摄取是通过网格蛋白介导的内吞和巨胞饮。此外，PC 12细胞来源的exosomes可以进入并递送microRNA（miRNAs）到骨髓来源的间充质基质细胞（BMSCs）中，并通过miR-21降低转化生长因子β受体II（TGF β RII）和原肌球蛋白-1（TPM 1）的表达水平。这些结果显示了外泌体内化的途径，并证明肿瘤细胞来源的外泌体调节正常细胞中的靶基因表达。
Exosomes are nanoscale membrane vesicles secreted from many types of cells. Carrying functional molecules, exosomes transfer information between cells and mediate many physiological and pathological processes. In this report, utilizing selective inhibitors, molecular tools, and specific endocytosis markers, the cellular uptake of PC12 cell-derived exosomes was imaged by high-throughput microscopy and statistically analyzed. It was found that the uptake was through clathrin-mediated endocytosis and macropinocytosis. Furthermore, PC12 cell-derived exosomes can enter and deliver microRNAs (miRNAs) into bone marrow-derived mesenchymal stromal cells (BMSCs), and decrease the expression level of transforming growth factor beta receptor II (TGF beta RII) and tropomyosin-1 (TPM1) through miR-21. These results show the pathway of exosome internalization and demonstrate that tumor cell-derived exosomes regulate target gene expression in normal cells.