期刊
JOURNAL OF EXTRACELLULAR VESICLES
卷 9, 期 1, 页码 -出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/20013078.2019.1706801
关键词
Astrocytes; extracellular vesicles; extracellular matrix; exosome; IL-1 beta; inflammatory diseases; neurodegenerative diseases; proteomics
类别
资金
- Cure Alzheimer's Fund
- BrightFocus Foundation [A2016551S]
- NIH [RF1AG054199, R01AG054672, R56AG057469, R21 NS104609]
- NIH from the Eunice Kennedy Shriver National Institute of Child Health & Human Development [5R24 HD0008836]
Astrocytes in the central nervous system (CNS) provide supportive neural functions and mediate inflammatory responses from microglia. Increasing evidence supports their critical roles in regulating brain homoeostasis in response to pro-inflammatory factors such as cytokines and pathogen/damage-associated molecular pattern molecules in infectious and neurodegenerative diseases. However, the underlying mechanisms of the trans-cellular communication are still unclear. Extracellular vesicles (EVs) can transfer a large diversity of molecules such as lipids, nucleic acids and proteins for cellular communications. The purpose of this study is to characterize the EVs cargo proteins derived from human primary astrocytes (ADEVs) under both physiological and pathophysiological conditions. ADEVs were isolated from human primary astrocytes after vehicle (CTL) or interleukin-1 beta (IL-1 beta) pre-treatment. Label-free quantitative proteomic profiling revealed a notable up-regulation of proteins including actin-associated molecules, integrins and major histocompatibility complex in IL-1 beta-ADEVs compared to CTL-ADEVs, which were involved in cellular metabolism and organization, cellular communication and inflammatory response. When fluorescently labelled ADEVs were added into primary cultured mouse cortical neurons, we found a significantly increased neuronal uptake of IL-1 beta-ADEVs compared to CTL-ADEVs. We further confirmed it is likely due to the enrichment of surface proteins in IL-1 beta-ADEVs, as IL-1 beta-ADEVs uptake by neurons was partially suppressed by a specific integrin inhibitor. Additionally, treatment of neurons with IL-1 beta-ADEVs also reduced neurite outgrowth, branching and neuronal firing. These findings provide insight for the molecular mechanism of the ADEVs' effects on neural uptake, neural differentiation and maturation, and its alteration in inflammatory conditions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据