VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway

doi:10.1111/cns.13400

科研成果详情

题名	VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway
作者	Sun, Zhezhe 1,2; Gu, Lei2,3; Wu, Ke 1,2; Wang, Kankai1,2; Ru, Junnan 1,2; Yang, Su 1,2; Wang, Zhenzhong 4; Zhuge, Qichuan1,2; Huang, Lijie1,2; Huang, Shengwei 1,2
发表日期	2020-09
发表期刊	CNS NEUROSCIENCE & THERAPEUTICS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	autophagy human umbilical mesenchymal stem cells stroke VX-765
其他关键词	UP-REGULATION ; TRANSPLANTATION ; NEUROPROTECTION ; MAINTENANCE ; INHIBITOR ; RECOVERY ; POTENT
摘要	Introduction To investigate the protective effect of VX-765 on human umbilical mesenchymal stem cells (HUMSCs) in stroke and its mechanism. Materials and methods Mouse models of ischemic stroke were established using the distal middle cerebral artery occlusion (dMCAO) method. The dMCAO mice were accordingly transplanted with HUMSCs, VX-765-treated HUMSCs, or VX-765 + MHY185-treated HUMSCs. The HUMSCs were inserted with green fluorescent protein (GFP) for measurement of transplantation efficiency which was determined by immunofluorescence assay. Oxygen-glucose deprivation (OGD) was applied to mimic ischemic environment in vitro experiments, and the HUMSCs herein were transfected with AMPK inhibitor Compound C or autophagy inhibitor 3-MA. MTT assay was used to test the toxicity of VX-765. TUNEL staining and ELISA were applied to measure the levels of apoptosis and inflammatory cytokines (IL-1 beta, IL-6, and IL-10), respectively. The expressions of autophagy-associated proteins, AMPK, and mTOR were detected by Western blotting. TTC staining was applied to reveal the infarct lesions in the brain of dMCAO mice. Results The pro-inflammatory cytokines, TUNEL-positive cells, and p-mTOR were decreased while the anti-inflammatory cytokine, autophagy-related proteins, and p-AMPK were increased in HUMSCs treated with VX-765 under OGD condition. Different expression patterns were found with the above factors after transfection of 3-MA or Compound C. The pro-inflammatory cytokines, TUNEL-positive cells, and infarct sections were decreased while the anti-inflammatory cytokine and autophagy-related proteins were increased in dMCAO mice transplanted with VX-765-treated HUMSCs compared to those transplanted with HUMSCs only. The autophagy was inhibited while p-mTOR was up-regulated after transfection of MHY. Conclusion VX-765 protects HUMSCs against stroke-induced apoptosis and inflammatory responses by activating autophagy via the AMPK/mTOR signaling pathway in vivo and in vitro.
资助项目	Wenzhou City Science and Technology Project [Y20180153, ZS2017007]; Natural Science Foundation of Ningbo [2018A610310]
出版者	WILEY
出版地	HOBOKEN
ISSN	1755-5930
EISSN	1755-5949
卷号	26 期号:9 页码:952-961
DOI	10.1111/cns.13400
页数	10
WOS类目	Neurosciences ; Pharmacology & Pharmacy
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy
WOS记录号	WOS:000535634700001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	32459063
PMC记录号	PMC7415204
SCOPUSEID	2-s2.0-85085572467
通讯作者地址	[Zhuge, Qichuan]Department of Neurosurgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China ; [Huang, Shengwei]Department of Neurosurgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China ; [Zhuge, Qichuan]Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research,Wenzhou Medical University,Wenzhou,China ; [Huang, Shengwei]Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology;Psychiatry and Mental Health;Physiology (medical);Pharmacology (medical)
引用统计	被引频次：16[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/16410
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_老化与神经疾病重点实验室第一临床医学院（信息与工程学院）、附属第一医院_内科学_神经内科
通讯作者	Zhuge, Qichuan; Huang, Shengwei
作者单位	1.Department of Neurosurgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research,Wenzhou Medical University,Wenzhou,China; 3.Department of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 4.Department of Neurosurgery,Yuyao people's Hospital,Ningbo,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 温州医科大学
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 温州医科大学
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Sun, Zhezhe,Gu, Lei,Wu, Ke,et al. VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway[J]. CNS NEUROSCIENCE & THERAPEUTICS,2020,26(9):952-961.
APA	Sun, Zhezhe., Gu, Lei., Wu, Ke., Wang, Kankai., Ru, Junnan., ... & Huang, Shengwei. (2020). VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway. CNS NEUROSCIENCE & THERAPEUTICS, 26(9), 952-961.
MLA	Sun, Zhezhe,et al."VX-765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke-induced apoptosis and inflammatory responses via AMPK/mTOR signaling pathway".CNS NEUROSCIENCE & THERAPEUTICS 26.9(2020):952-961.