Exosomes-mediated phenotypic switch of macrophages in the immune microenvironment after spinal cord injury
Autor: | Hao Yu, Peng Peng, Cong Xing, Bo Tao, Jingyuan Huang, Shiqing Feng, Chao Li, Guangzhi Ning, Bin Zhang |
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Rok vydání: | 2021 |
Předmět: |
Male
Cell Plasticity Macrophage polarization Spinal cord injury RM1-950 Exosomes MiRNA-mRNA network Mice Animals Macrophage PTEN Rats Wistar Protein kinase B Spinal Cord Injuries PI3K/AKT/mTOR pathway Pharmacology biology Macrophages PTEN Phosphohydrolase General Medicine M2 Macrophage Microvesicles Cell biology Mice Inbred C57BL Disease Models Animal MicroRNAs Phenotype RAW 264.7 Cells Immune microenvironment Cellular Microenvironment Spinal Cord biology.protein Therapeutics. Pharmacology Phosphatidylinositol 3-Kinase Proto-Oncogene Proteins c-akt Reprogramming Signal Transduction |
Zdroj: | Biomedicine & Pharmacotherapy, Vol 144, Iss, Pp 112311-(2021) |
ISSN: | 0753-3322 |
Popis: | Although accumulating evidence indicated that modulating macrophage polarization could ameliorate the immune microenvironment and facilitate the repair of spinal cord injury (SCI), the underlying mechanism of macrophage phenotypic switch is still poorly understood. Exosomes (Exos), a potential tool of cell-to-cell communication, may play important roles in cell reprogramming. Herein, we investigated the roles of macrophages-derived exosomes played for macrophage polarization in the SCI immune microenvironment. In this study, we found the fraction of M2 macrophages was markedly decreased after SCI. Moreover, the M2 macrophages-derived exosomes could increase the percentage of M2 macrophages, decrease that of M1 macrophages while the M1 macrophages-derived exosomes acted oppositely. According to the results of in silico analyses and molecular experiments verification, this phenotypic switch might be mediated by the exosomal miRNA-mRNA network, in which the miR-23a-3p/PTEN/PI3K/AKT axis might play an important role. In conclusion, our study suggests macrophage polarization that regulated by various interventions might be mediated by their own exosomes at last. Moreover, M2 macrophages-derived exosomes could promote M2 macrophage polarization via the potential miRNA-mRNA network. Considering its potential of modulating polarization, M2 macrophages-derived exosomes may be a promising therapeutic agent for SCI repair. |
Databáze: | OpenAIRE |
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