Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Protect Liver Ischemia/Reperfusion Injury by Reducing CD154 Expression on CD4+ T Cells via CCT2.
Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Protect Liver Ischemia/Reperfusion Injury by Reducing CD154 Expression on CD4+ T Cells via CCT2.
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人脐带间充质干细胞衍生的细胞外囊泡通过 CCT2 减少 CD4 T 细胞上 CD154 的表达来保护肝脏缺血/再灌注损伤
DOI：
10.1002/advs.201903746
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Zheng J;Lu T;Zhou C;Cai J;Zhang X;Liang J;Sui X;Chen X;Chen L;Sun Y;Zhang J;Chen W;Zhang Y;Yao J;Chen G;Yang Y
肝缺血再灌注损伤(IRI)作为肝移植术后并发症和早期肝功能衰竭的原因之一，在临床应用中尚无有效的治疗方法。尽管骨髓间充质干细胞(MSCs)对肝脏IRI的治疗潜力已被证明，但其潜在的机制尚不完全清楚。MSC来源的胞外小泡(MSC-EVS)是新近发现的细胞间通讯信使。在此，有报道称脐带源MSCs(UC-MSCs)通过其分泌的EV改善小鼠肝脏IRI。再灌流6h后UC-MSC-EVS主要集中在肝脏。此外，UC-MSC-EVS可显著调节肝内CD4+T细胞膜CD154的表达，从而启动肝脏炎症反应，加重肝脏IRI。从机制上讲，蛋白质质谱分析表明，含有TCP1亚单位2的伴侣蛋白(CCT2)在UC-MSC-EVS中富含，它调节钙通道影响钙离子内流，抑制CD4+T细胞CD154的合成。总之，这些结果突出了UC-MSC-EVS在减轻肝脏IRI方面的治疗潜力。这一发现提示UC-MSC-EVS来源的CCT2可通过钙-钙调神经磷酸酶-NFAT1信号通路调节肝脏IRI时肝内CD4+T细胞CD154的表达。
As a cause of postoperative complications and early hepatic failure after liver transplantation, liver ischemia/reperfusion injury (IRI) still has no effective treatment during clinical administration. Although the therapeutic potential of mesenchymal stem cells (MSCs) for liver IRI has been previously shown, the underlying mechanisms are not completely clear. It is accepted that MSC‐derived extracellular vesicles (MSC‐EVs) are newly uncovered messengers for intercellular communication. Herein, it is reported that umbilical cord‐derived MSCs (UC‐MSCs) improve liver IRI in mice through their secreted EVs. It is also visualized that UC‐MSC‐EVs mainly concentrate in liver after 6 h of reperfusion. Furthermore, UC‐MSC‐EVs are found to significantly modulate the membranous expression of CD154 of intrahepatic CD4+ T cells, which is an initiation of inflammatory response in liver and can aggravate liver IRI. Mechanistically, protein mass spectrum analysis is performed and it is revealed that Chaperonin containing TCP1 subunit 2 (CCT2) enriches in UC‐MSC‐EVs, which regulates the calcium channels to affect Ca2+ influx and suppress CD154 synthesis in CD4+ T cells. In conclusion, these results highlight the therapeutic potential of UC‐MSC‐EVs in attenuating liver IRI. This finding suggests that CCT2 from UC‐MSC‐EVs can modulate CD154 expression of intrahepatic CD4+ T cells during liver IRI through the Ca2+‐calcineurin‐NFAT1 signaling pathway.
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影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
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影响因子：
11.4
作者：
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作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
9.8
作者：
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通讯作者：
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