PMID- 33461167
OWN - NLM
STAT- MEDLINE
DCOM- 20210816
LR  - 20210816
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 13
IP  - 3
DP  - 2021 Jan 10
TI  - Microglia exosomal miRNA-137 attenuates ischemic brain injury through targeting 
      Notch1.
PG  - 4079-4095
LID - 10.18632/aging.202373 [doi]
AB  - Microglia are the resident immune cells in the central nervous system and play an 
      essential role in brain homeostasis and neuroprotection in brain diseases. 
      Exosomes are crucial in intercellular communication by transporting bioactive 
      miRNAs. Thus, this study aimed to investigate the function of microglial exosome 
      in the presence of ischemic injury and related mechanism. Oxygen-glucose 
      deprivation (OGD)-treated neurons and transient middle cerebral artery occlusion 
      (TMCAO)-treated mice were applied in this study. Western blotting, RT-PCR, 
      RNA-seq, luciferase reporter assay, transmission electron microscope, 
      nanoparticle tracking analysis, immunohistochemistry, TUNEL and LDH assays, and 
      behavioral assay were applied in mechanistic and functional studies. The results 
      demonstrated that exosomes derived from microglia in M2 phenotype (BV2-Exo) were 
      internalized by neurons and attenuated neuronal apoptosis in response to ischemic 
      injury in vitro and in vivo. BV2-Exo also decreased infarct volume and behavioral 
      deficits in ischemic mice. Exosomal miRNA-137 was upregulated in BV2-Exo and 
      participated in the partial neuroprotective effect of BV2-Exo. Furthermore, 
      Notch1 was a directly targeting gene of exosomal miRNA-137. In conclusion, these 
      results suggest that BV2-Exo alleviates ischemia-reperfusion brain injury through 
      transporting exosomal miRNA-137. This study provides novel insight into 
      microglial exosomes-based therapies for the treatment of ischemic brain injury.
FAU - Zhang, Dianquan
AU  - Zhang D
AD  - Department of Rehabilitation Medicine, Shenzhen Longhua District Central 
      Hospital, Shenzhen, China.
FAU - Cai, Guoliang
AU  - Cai G
AD  - Postdoctoral Research Workstation of Harbin Sport University, Harbin 150008, 
      China.
AD  - Harbin Sport University, Harbin 150008, China.
FAU - Liu, Kai
AU  - Liu K
AD  - Hanan Branch of Second Affiliated Hospital of Heilongjiang University of 
      Traditional Chinese Medicine, Harbin 150001, China.
FAU - Zhuang, Zhe
AU  - Zhuang Z
AD  - Second Affiliated Hospital of Heilongjiang University of Traditional Chinese 
      Medicine, Harbin 150001, China.
FAU - Jia, Kunping
AU  - Jia K
AD  - Hanan Branch of Second Affiliated Hospital of Heilongjiang University of 
      Traditional Chinese Medicine, Harbin 150001, China.
FAU - Pei, Siying
AU  - Pei S
AD  - Hanan Branch of Second Affiliated Hospital of Heilongjiang University of 
      Traditional Chinese Medicine, Harbin 150001, China.
FAU - Wang, Xiuzhen
AU  - Wang X
AD  - Hanan Branch of Second Affiliated Hospital of Heilongjiang University of 
      Traditional Chinese Medicine, Harbin 150001, China.
FAU - Wang, Hong
AU  - Wang H
AD  - Hanan Branch of Second Affiliated Hospital of Heilongjiang University of 
      Traditional Chinese Medicine, Harbin 150001, China.
FAU - Xu, Shengnan
AU  - Xu S
AD  - Heilongjiang University of Traditional Chinese Medicine, Harbin, China.
FAU - Cui, Cheng
AU  - Cui C
AD  - Heilongjiang University of Traditional Chinese Medicine, Harbin, China.
FAU - Sun, Manchao
AU  - Sun M
AD  - Heilongjiang University of Traditional Chinese Medicine, Harbin, China.
FAU - Guo, Sihui
AU  - Guo S
AD  - Heilongjiang University of Traditional Chinese Medicine, Harbin, China.
FAU - Song, Wenli
AU  - Song W
AD  - Harbin Sport University, Harbin 150008, China.
FAU - Cai, Guofeng
AU  - Cai G
AD  - Hanan Branch of Second Affiliated Hospital of Heilongjiang University of 
      Traditional Chinese Medicine, Harbin 150001, China.
AD  - Postdoctoral Research Station of Heilongjiang Academy of Traditional Chinese 
      Medicine, Harbin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210110
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (MIRN137 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Notch1 protein, mouse)
RN  - 0 (Receptor, Notch1)
SB  - IM
MH  - Animals
MH  - Apoptosis/*genetics
MH  - Brain Ischemia/*genetics/metabolism/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Exosomes/*metabolism
MH  - Infarction, Middle Cerebral Artery/genetics/pathology/physiopathology
MH  - Mice
MH  - MicroRNAs/*genetics/metabolism
MH  - Microglia/*metabolism
MH  - Neurons/*metabolism
MH  - Neuroprotection/genetics
MH  - Receptor, Notch1
MH  - Reperfusion Injury/*genetics/metabolism/pathology/physiopathology
PMC - PMC7906161
OTO - NOTNLM
OT  - Notch1
OT  - exosome
OT  - ischemic injury
OT  - miRNA-137
OT  - microglia
COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of 
      interest.
EDAT- 2021/01/19 06:00
MHDA- 2021/08/17 06:00
PMCR- 2021/02/15
CRDT- 2021/01/18 20:17
PHST- 2020/04/21 00:00 [received]
PHST- 2020/09/28 00:00 [accepted]
PHST- 2021/01/19 06:00 [pubmed]
PHST- 2021/08/17 06:00 [medline]
PHST- 2021/01/18 20:17 [entrez]
PHST- 2021/02/15 00:00 [pmc-release]
AID - 202373 [pii]
AID - 10.18632/aging.202373 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2021 Jan 10;13(3):4079-4095. doi: 10.18632/aging.202373. Epub 
      2021 Jan 10.