Microglia Activated by α-Synuclein Inhibits Autophagy in SH-SY5Y Cells by Transporting miR-19a-3p Via Exosomes
- VernacularTitle:被α-synuclein激活的小胶质细胞通过外泌体转运miR-19a-3p抑制神经细胞自噬
- Author:
Hui LIN
1
;
Si-qi LIU
2
;
Yun-yuan HUANG
2
;
Tian-en ZHOU
3
Author Information
1. Department of Internal Medicine， South China Agricultural University Hospital， Guangzhou 510640， China
2. Department of Emergency， SunYat-sen Memorial Hospital， SunYat-sen University， Guangzhou 510120， China
3. Department of Emergency， The Affiliated Foshan Hospital of Sun Yat-sen University， Foshan 528000， China
- Publication Type:Journal Article
- Keywords:
α-synuclein;
exosome;
miR-19a-3p;
autophagy;
microglia;
SH-SY5Y cells
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(1):57-65
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the changes of miRNAs in exosomes secreted from microglia after being activated by exosomes of SH-SY5Y cells overexpressing α-synuclein （SNCA-HM Exo） and their effects on autophagy of SH-SY5Y cells． MethodsMicroglia exosomes were collected for miRNAs microarray analysis and PCR detection， and the differentially expressed miRNAs were screened out. Their target genes were analyzed by Kyoto Encyclopedia of Genes and Genomes （KEGG） and Gene Ontology （GO）. MiRNAs and their target genes related to PI3K/Akt/signaling pathway were screened out and verified by Western blot. The SH-SY5Y cells were divided into four groups：Con-HM Exo，Con-HM Exo+miR-19a mimic，SNCA-HM Exo and SNCA-HM Exo+miR-19a-3p inhibitor. ResultsFifteen differentially expressed miRNAs were screened out by microarray analysis and PCR. KEGG and GO analysis showed that PI3K/Akt signaling pathway had the highest enrichment score of target genes， and PTEN was one of the target genes regulated by mir-19a-3p. We found that， compared with the control group， the expression of PTEN and LC3 Ⅱ/I were decreased， while the expression of p-Akt/Akt， p-mTOR/mTOR and p62 were increased in the miR-19a-3p mimic group and the SNCA-HM Exo group （P < 0.05）. However， miR-19a-3p inhibitor could reverse this effect （P < 0.05）. ConclusionSNCA-HM Exo regulates PTEN through miR-19a-3p， activates PI3K/Akt/mTOR signaling pathway， and then inhibits autophagy in SH-SY5Y cells．
