AccScience Publishing / AN / Online First / DOI: 10.36922/an.3166
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ORIGINAL RESEARCH ARTICLE

Proteomic analysis of exosomes derived from detrimental and protective microglia

Lingyun Bai1 ,  Fangyu Chen2 ,  Shengnan Xia2 ,  Xiang Cao1,2,3*
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1 Department of Neurology, Joint Institute of Nanjing Drum Tower Hospital for Life and Health, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, China
2 Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
3 State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu, China
Advanced Neurology 2024, 3(3), 3166 https://doi.org/10.36922/an.3166
Submitted: 14 March 2024 | Accepted: 14 June 2024 | Published: 7 August 2024
(This article belongs to the Special Issue Advances in stroke research and therapy)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Microglia, the primary resident immune cells in the brain, exhibit two distinct functional states: The detrimental (M1) phenotype and the protective (M2) phenotype. Exosomes, which are released by various cell types, play crucial roles in intercellular communication. While existing studies have shown that exosomes from microglia with different activation states can affect neuronal survival following ischemic stroke, a comprehensive exploration of the differences between these microglial phenotypes is still lacking. In this study, we treated primary microglia with lipopolysaccharide(LPS) or interleukin-4 (IL-4) to induce the M1 or M2 phenotype, respectively, and investigated the characteristics of the resulting exosomes. These microglia-derived exosomes can be internalized by neurons. Specifically, exosomes derived from M1microglia (M1-EXOs) exacerbated ischemia-induced neuronal apoptosis both in vivo and in vitro, while exosomes from M2 microglia (M2-EXOs) exhibited a protective effect. Subsequently, we conducted a quantitative proteomic analysis of M1-EXOsand M2-EXOs, characterizing 1129 proteins. Notably, M1-EXO proteins were primarily associated with inflammatory responses, neutrophil chemotaxis, and complement activation. In contrast, M2-EXO proteins were predominantly involved in protein transport and cellular proliferation. In addition, we analyzed key proteins, includingIL-6, SAA3, CCL5, CCL9, C3, CFB, SRGN, and sphingosine-1-phosphate phosphatase 1,which play central roles in the protein-protein interaction network. Overall, this dataset provides valuable insights into the proteomic profiles of exosomes derived from microglia with distinct phenotypes, enhancing our understanding of the mechanisms underlying microglial involvement in central nervous system diseases.

Keywords
Microglia
Exosomal proteins
Ischemic stroke
Proteomics
Funding
This research was supported by the National Natural Science Foundation of China (82371326, 82171310), Jiangsu Provincial ‘333’ High-level Talent Training Project Funding.
Conflict of interest
The authors declare no conflicts of interest.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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