小胶质细胞
自噬
微泡
细胞生物学
灯1
MAPK/ERK通路
绿色荧光蛋白
生物
炎症
小RNA
分子生物学
化学
信号转导
免疫学
基因
细胞凋亡
生物化学
作者
Tianen Zhou,Meng Zhang,Yingyu Xie,Ying Chen,Sheng Peng,Xin Jing,Ming Lei,Enxiang Tao,Yucheng Liang
标识
DOI:10.1016/j.cellsig.2021.110179
摘要
Our previous study has revealed that GFP-α-synuclein overexpressing SH-SY5Y cells-derived exosomes (GFP-SNCA Exo) decrease autophagy in microglia via their load of miRNAs. However, it is unclear whether GFP-SNCA Exo can affect microglial inflammation via modulation of autophagy. In order to investigate the effects of miRNAs carried by GFP-SNCA Exo on autophagy and inflammation of microglia. SH-SY5Y cells were transfected with lentivirus expressing α-synuclein and then their exosomes were collected. Western blot and laser confocal images showed that α-synuclein transferred between SH-SY5Y cells and microglia through exosomes. Differentially expressed miRNAs between GFP-SNCA Exo and the vector exosomes were detected by microarray analysis. After bioinformatics analysis of the differentially expressed miRNAs, we found that their target genes were enriched in the MAPK and autophagy-associated signaling pathway. The expression of P62, p-JNK/JNK, and p-ERK/ERK and the release of IL-6 significantly increased whereas LC3 II/I decreased in microglia exposed to GFP-SNCA Exo for 48 h when compared to the control group. But rapamycin could reverse the increasing expression of p-JNK/JNK, p-ERK/ERK and the release of IL-6 induced by GFP-SNCA Exo. Dual immunofluorescence staining for LC3B and LAMP1 showed that the fluorescence density of LC3B decreased and the fluorescence of LC3B and LAMP1 were not co-located in microglia after 48 h co-culture with GFP-SNCA Exo compared with the control group, which indicated that these exosomes decreased autophagy and impaired the autophagy flux in recipient microglia. Taken together, our results indicate that GFP-SNCA Exo activate the MAPK signaling pathway and inflammation by decreasing autophagy in microglia.
科研通智能强力驱动
Strongly Powered by AbleSci AI