hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury
hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury
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HucMSC 外泌体衍生的 GPX1 是肝氧化损伤恢复所必需的
DOI：
10.1016/j.ymthe.2016.11.019
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发表时间：
2017-02-01
影响因子：
12.4
通讯作者：
Xu, Wenrong
中科院分区：
文献类型：
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作者：
Yan, Yongmin;Jiang, Wenqian;Xu, Wenrong
外泌体是由各种细胞分泌的小生物膜囊泡，包括间充质干细胞（MSCs）。我们之前报道过msc来源的外泌体（MSC-Ex）可以引起肝脏保护作用，对抗毒物性损伤。然而，以msc - ex为基础的治疗肝脏疾病的成功及其潜在机制尚未得到很好的表征。我们使用不同剂量的人脐带间充质干细胞衍生外泌体（hucMSC-Ex）通过尾静脉或口服灌胃给药，并在移植肝小鼠模型中观察到抗氧化和抗凋亡作用以及对肝衰竭的拯救作用。单次系统给予humsc - ex （16 mg/ kg）有效地挽救了四氯化碳（CCl4）诱导的肝衰竭小鼠。此外，解毒CCl4和H2O2的hucmsc - ex衍生谷胱甘肽过氧化物酶1 （GPX1）可减少氧化应激和细胞凋亡。在体外和体内实验中，敲低GPX1可降低humsc - ex的抗氧化和抗凋亡能力，降低其肝保护作用。因此，hucMSC-Ex通过传递GPX1促进肝氧化损伤的恢复。
Exosomes are small biological membrane vesicles secreted by various cells, including mesenchymal stem cells (MSCs). We previously reported that MSC-derived exosomes (MSC-Ex) can elicit hepatoprotective effects against toxicant-induced injury. However, the success of MSC-Ex-based therapy for treatment of liver diseases and the underlying mechanisms have not been well characterized. We used human umbilical cord MSC-derived exosome (hucMSC-Ex) administrated by tail vein or oral gavage at different doses and, in engrafted liver mouse models, noted antioxidant and anti-apoptotic effects and rescue from liver failure. A single systemic administration of hucMSC-Ex (16 mg/ kg) effectively rescued the recipient mice from carbon tetrachloride (CCl4)-induced liver failure. Moreover, hucMSC-Ex-derived glutathione peroxidase1 (GPX1), which detoxifies CCl4 and H2O2, reduced oxidative stress and apoptosis. Knockdown of GPX1 in hucMSCs abrogated antioxidant and anti-apoptotic abilities of hucMSC-Ex and diminished the hepatoprotective effects of hucMSC-Ex in vitro and in vivo. Thus, hucMSC-Ex promote the recovery of hepatic oxidant injury through the delivery of GPX1.