title: hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury.
abstract: 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 CCl4and 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.
authors.affiliation: Liver Disease and Cancer Institute, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China. Electronic address: ujsyym@163.com.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Liver Disease and Cancer Institute, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Jiang
authors.affiliation: The Affiliated Third Hospital of Zhenjiang, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Tan
authors.affiliation: The Affiliated Third Hospital of Zhenjiang, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Shengqiang
authors.initials: S
authors.lastname: Zou
authors.affiliation: The Affiliated Third Hospital of Zhenjiang, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Liver Disease and Cancer Institute, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Mao
authors.affiliation: Liver Disease and Cancer Institute, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gong
authors.affiliation: Liver Disease and Cancer Institute, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China; Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.affiliation: Liver Disease and Cancer Institute, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China; Key Laboratory of Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, People's Republic of China. Electronic address: icls@ujs.edu.cn.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D055354:Exosomes / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D017093:Liver Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D015398:Signal Transduction; D014470:Umbilical Cord / Q000166:cytology*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D016877:Oxidants; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1
keywords: exosome; glutathione peroxidase1; hepatic injury; mesenchymal stem cell; oxidative stress