Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p
Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p
复制标题
慢性硬膜下血肿血肿来源的外泌体通过miR-144-5p促进异常血管生成并抑制血肿吸收
DOI：
10.18632/aging.102550
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发表时间：
2019-12-31
期刊：
影响因子：
5.2
通讯作者：
Jiang, Rongcai
中科院分区：
文献类型：
--
作者：
Gao, Chuang;Gong, Zhitao;Jiang, Rongcai
外泌体是一种小的（直径30- 150nm）脂质双层封闭的囊泡，存在于所有体液中。我们研究了外泌体是否在慢性硬膜下血肿（CSDH）中起作用。外泌体通过透射电子显微镜和NanoSight颗粒跟踪进行鉴定和表征。在急性硬膜下血肿（SDH）大鼠模型中评估血肿源性外泌体的功能。血肿源性外泌体抑制血肿吸收，加重SDH大鼠的神经功能缺损。我们研究了外泌体对人脐静脉内皮细胞（HUVECs）血管生成和细胞通透性的影响。外泌体与HUVECs共培养表明血肿来源的外泌体被HUVECs吸收，导致管形成和血管通透性增强。此外，伴有ANG-2表达升高和ANG-1表达降低。外泌体富含包括miR-144-5p在内的microrna，它们可以将其传递给HUVECs以促进血管生成并增加膜通透性。在HUVECs和SDH大鼠中，miR-144-5p的过表达促进了异常血管生成和血肿吸收的减少，这在体外和体内都模拟了血肿源性外泌体的作用。因此，血肿源性外泌体通过CSDH中的miR-144-5p促进高通透性的异常血管生成，抑制血肿吸收。
Exosomes are small (30-150 nm diameter) lipid bilayer-enclosed vesicles found in all bodily fluids. We investigated whether exosomes play a role in chronic subdural hematoma (CSDH). Exosomes were identified and characterized using transmission electron microscopy and NanoSight particle tracking. The functions of hematoma-derived exosomes were evaluated in a rat model of acute subdural hematoma (SDH). The hematoma-derived exosomes inhibited hematoma absorption and exacerbated neurological deficits in SDH rats. We examined the effects of the exosomes on angiogenesis and cell permeability in human umbilical vein endothelial cells (HUVECs). Co-culture of exosomes with HUVECs revealed that the hematoma-derived exosomes were taken-in by the HUVECs, resulting in enhanced tube formation and vascular permeability. Additionally, there was a concomitant increase in ANG-2 expression and decrease in ANG-1 expression. Exosomes were enriched with microRNAs including miR-144-5p, which they could deliver to HUVECs to promote angiogenesis and increase membrane permeability. Overexpression of miR-144-5p in HUVECs and in SDH rats promoted abnormal angiogenesis and reduced hematoma absorption, which mimicked the effects of the hematoma-derived exosomes both in vitro and in vivo. Thus, hematoma-derived exosomes promote abnormal angiogenesis with high permeability and inhibit hematoma absorption through miR-144-5p in CSDH.