PMID- 37812019
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20240118
IS  - 1563-5260 (Electronic)
IS  - 0167-7063 (Linking)
VI  - 37
IP  - 3
DP  - 2023 Sep
TI  - Neural stem cell-derived exosomal FTO protects neuron from microglial 
      inflammatory injury by inhibiting microglia NRF2 mRNA m6A modification.
PG  - 103-114
LID - 10.1080/01677063.2023.2259995 [doi]
AB  - Ischemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes 
      derived from neural stem cells (NSC-Exos) improve neural plasticity and promote 
      neural function repair following IS. However, the potential mechanism remains 
      unclear. In this study, NSC-Exos were characterized and co-cultured with 
      microglia. We found that NSC-Exos increased NRF2 expression in oxygen-glucose 
      deprivation/reoxygenation and LPS-induced microglia and converted microglia from 
      M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. NSC-Exos reduced 
      m6A methylation modification of nuclear factor erythroid 2-related factor 2 
      (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, NSC-Exos reduced the 
      damage to neurons caused by microglia's inflammatory response. Finally, the 
      changes in microglia polarization and neuron damage caused by FTO knockdown in 
      NSE-Exos were attenuated by NRF2 overexpression in microglia. These findings 
      revealed that NSC-Exos promotes NRF2 expression and M2 polarization of microglial 
      via transferring FTO, thereby resulting in neuroprotective effects.
FAU - Li, Zhiyong
AU  - Li Z
AD  - Medical Quality Management Department, The First Affiliated Hospital of Hainan 
      Medical College, Haikou, Hainan, China.
FAU - Chen, Zhenggang
AU  - Chen Z
AD  - Neurosurgery Department, The First Affiliated Hospital of Hainan Medical College, 
      Haikou, Hainan, China.
FAU - Peng, Jun
AU  - Peng J
AD  - Neurosurgery Department, Haikou Affiliated Hospital of Central South University 
      Xiangya School of Medicine, Haikou, Hainan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231016
PL  - England
TA  - J Neurogenet
JT  - Journal of neurogenetics
JID - 8406473
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.14.11.33 (FTO protein, human)
RN  - EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
SB  - IM
MH  - Humans
MH  - Microglia/metabolism
MH  - NF-E2-Related Factor 2/genetics/metabolism/pharmacology
MH  - *Brain Ischemia/metabolism
MH  - Neurons/metabolism
MH  - *Neural Stem Cells
MH  - Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism
OTO - NOTNLM
OT  - FTO
OT  - NRF2
OT  - NSC-Exos
OT  - m6A
EDAT- 2023/10/09 12:43
MHDA- 2023/11/02 12:45
CRDT- 2023/10/09 09:23
PHST- 2023/11/02 12:45 [medline]
PHST- 2023/10/09 12:43 [pubmed]
PHST- 2023/10/09 09:23 [entrez]
AID - 10.1080/01677063.2023.2259995 [doi]
PST - ppublish
SO  - J Neurogenet. 2023 Sep;37(3):103-114. doi: 10.1080/01677063.2023.2259995. Epub 
      2023 Oct 16.