Protective role of microRNA-27a upregulation and HSP90 silencing against cerebral ischemia-reperfusion injury in rats by activating PI3K/AKT/mTOR signaling pathway.
Animals
Apoptosis
/ genetics
Behavior, Animal
Brain
/ metabolism
Cytokines
/ blood
Disease Models, Animal
Gene Silencing
Glutathione
/ metabolism
HSP90 Heat-Shock Proteins
/ genetics
Malondialdehyde
/ metabolism
MicroRNAs
/ genetics
Oxidative Stress
/ genetics
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Rats, Wistar
Reperfusion Injury
/ genetics
Signal Transduction
Superoxide Dismutase
/ metabolism
TOR Serine-Threonine Kinases
/ metabolism
Up-Regulation
Cerebral ischemia–reperfusion injury
Heat shock protein 90
Inflammatory response
MicroRNA-27a
Oxidative stress
Phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
25
09
2019
revised:
12
05
2020
accepted:
22
05
2020
pubmed:
8
7
2020
medline:
29
5
2021
entrez:
8
7
2020
Statut:
ppublish
Résumé
MicroRNAs (miRNAs) have been reported in cerebral ischemia-reperfusion injury, yet the function of miR-27a in it has seldom been mentioned. This study aims to assess the mechanisms of miR-27a in rats with cerebral ischemia-reperfusion injury. The cerebral ischemia-reperfusion models of rat pups were established by bilateral carotid artery occlusion. Rats were treated with miR-27a agomir, silenced HSP90 expression plasmids or PI3K/AKT/mTOR pathway agonist. Oxidative stress indices, inflammatory factors, brain tissue water content, cerebral infarct volume, neurological function score and neuronal apoptosis in rats with cerebral ischemia-reperfusion injury were measured. MiR-27a and HSP90 expression and PI3K/AKT/mTOR phosphorylation levels in the brain tissues of rats were also detected. MiR-27a expression and PI3K/AKT/mTOR phosphorylation levels were downregulated while HSP90 expression was upregulated in cerebral ischemia-reperfusion injury rats. Elevated miR-27a or reduced HSP90 diminished water content, neuronal apoptosis and infarct volume, suppressed oxidative stress and inflammatory response, as well as improved neurological deficits and pathological damages. Moreover, elevated miR-27a or silenced HSP90 upregulated PI3K/AKT/mTOR phosphorylation levels in cerebral ischemia-reperfusion injury rats. HSP90 silencing or PI3K/AKT/mTOR pathway agonist reversed the unfavorable effects of low miR-27a expression on cerebral ischemia-reperfusion injury rats. To conclude, our study demonstrates that elevated miR-27a or decreased HSP90 attenuates oxidative stress and inflammatory response, and improves neurological function in cerebral ischemia-reperfusion injury rats by activating PI3K/AKT/mTOR signaling pathway.
Identifiants
pubmed: 32634698
pii: S1567-5769(19)32132-0
doi: 10.1016/j.intimp.2020.106635
pii:
doi:
Substances chimiques
Cytokines
0
HSP90 Heat-Shock Proteins
0
MIRN27 microRNA, rat
0
MicroRNAs
0
Malondialdehyde
4Y8F71G49Q
Superoxide Dismutase
EC 1.15.1.1
mTOR protein, rat
EC 2.7.1.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Glutathione
GAN16C9B8O
Types de publication
Journal Article
Retracted Publication
Langues
eng
Sous-ensembles de citation
IM
Pagination
106635Commentaires et corrections
Type : RetractionIn
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflicts of interest.