DOI: 10.1002/ame2.12394
Neural stem cell-derived exosomes regulate cell proliferation,migration,and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia
Xiaojun Deng1
Xiaoyi Hu2
Shang Wang2
Hui Zhao3
Yaqin Wei2
Jiaqi Fu3
Wenhui Wu2
Jinming Liu2
Caicai Zhang4
Lili Wang5
Ping Yuan2
1.Department of Critical Care Medicine,Shanghai Sixth People's Hospital,Shanghai Jiao Tong University,Shanghai,China2.Department of Cardio-Pulmonary Circulation,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai,China3.Institute of Bismuth Science,University of Shanghai for Science and Technology,Shanghai,China4.Department of Physiology,Hainan Medical University Haikou,Hainan,China5.Department of Clinical Medical Laboratory Center,Hangzhou Red Cross Hospital,Zhejiang,China
摘要：Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.
Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.
Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.
Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.
机标关键词：exosomeshypoxiastembraincellsaxiscell-deriveddeath
论文发表日期：2024-02-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 24-35 )
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