动物模型与实验医学(英文)2024，Vol.7Issue(1) ：24-35.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 Deng Xiaoyi Hu Shang Wang Hui Zhao Yaqin Wei Jiaqi Fu Wenhui Wu Jinming Liu Caicai Zhang Lili Wang Ping Yuan
动物模型与实验医学(英文)2024，Vol.7Issue(1) ：24-35.DOI:10.1002/ame2.12394
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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 Deng 1Xiaoyi Hu 2Shang Wang 2Hui Zhao 3Yaqin Wei 2Jiaqi Fu 3Wenhui Wu 2Jinming Liu 2Caicai Zhang 4Lili Wang 5Ping Yuan2
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作者信息

  • 1. Department of Critical Care Medicine,Shanghai Sixth People's Hospital,Shanghai Jiao Tong University,Shanghai,China
  • 2. Department of Cardio-Pulmonary Circulation,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai,China
  • 3. Institute of Bismuth Science,University of Shanghai for Science and Technology,Shanghai,China
  • 4. Department of Physiology,Hainan Medical University Haikou,Hainan,China
  • 5. Department of Clinical Medical Laboratory Center,Hangzhou Red Cross Hospital,Zhejiang,China
  • 折叠

Abstract

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.

Key words

brain microvascular endothelial cells/exosomes/Hes1/miR-9/neural stem cells

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基金项目

Program of Natural Science Foundation of Shanghai(21ZR1453800)

Program of Natural Science Foundation of Shanghai(22ZR1452400)

Program of National Natural Science Foundation of China(82370057)

中央高校基本科研业务费专项(22120220562)

Program of Shanghai Municipal Health Commission(20204Y0384)

Program of National Key Research and Development Project of China(2023YFC2509500)

Pujiang Talent Program(22PJD064)

Program of Shanghai Sixth People's Hospital Level Scientific Research Fund(DY2019003)

Program of Shanghai Sixth People's Hospital Level Scientific Research Fund(ynhg202123)

Program of Shanghai Pulmonary Hospital(FKLY20005)

Program of Shanghai Pulmonary Hospital(fkzr2320)

Program of Shanghai Pulmonary Hospital(fk18003)

出版年

2024
动物模型与实验医学(英文)
中国实验动物学会,中国医学科学院医学实验动物研究所

动物模型与实验医学(英文)

ISSN：2096-5451
参考文献量32
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