Neuron-derived exosomes with high miR-21-5p expression promoted polarization of M1 microglia in culture
Abstract
Background Neuroinflammation is a characteristic pathological change of acute neurological deficit and chronic traumatic encephalopathy (CTE) after traumatic brain injury (TBI). Microglia are the key cell involved in neuroinflammation and neuronal injury. The type of microglia polarization determines the direction of neuroinflammation. MiR-21-5p elevated in neurons and microglia after TBI in our previous research. In this study, we explore the influence of miR-21-5p for neuroinflammation by regulating microglia polarization. Methods In this study, PC12 and BV2 used to instead of neuron and microglia respectively. The co-cultured transwell system used to simulate interaction of PC12 and BV2 cells in vivo environment. Results We found that PC12-derived exosomes with containing miR-21-5p were phagocytosed by microglia and induced microglia polarization, meanwhile, the expression of miR-21-5p was increased in M1 microglia cells. Polarization of M1 microglia aggravated the release of neuroinflammation factors, inhibited the neurite outgrowth, increased accumulation of P-tau and promoted the apoptosis of PC12 cells, which formed a model of cyclic cumulative damage. Simultaneously, we also got similar results in vivo experiments. Conclusions PC12-derived exosomes with containing miR-21-5p is the essential of this cyclic cumulative damage model. Therefore, regulating the expression of miR-21-5p or the secretion of exosomes may be an important novel strategy for the treatment of neuro…
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Elevation of miR-21 leads to microglial pro-inflammatory polarization in diverse pathological contexts.
“the elevation of miR-21 led to microglial pro-inflammatory polarization in diverse pathological contexts [39,60,61,62].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [61]
Exosomal miRNA cargo may depend on intracellular miRNA levels and active/passive transference.
“We have previously shown that exosomal miRNA cargo may depend on intracellular miRNA levels and active/passive transference [39,61,62].”
From Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease (2022) · cites this paper as [61]
Exosomal delivery of overexpressed miR-21-5p to BV2 microglia promotes M1 polarization, and subsequent release of pro-inflammatory factors inhibits neurite outgrowth, increases P-tau accumulation, promotes PC12 apoptosis, and aggravates damage.
“Overexpressed miR-21-5p was delivered using exosomes to BV2 microglia cells and promoted M1 polarization (mirrored by iNOS activity). Subsequent release of pro-inflammatory factors inhibited neurite outgrowth, increased accumulation of P-tau and promoted the apoptosis of PC12 cells, thus aggravating the damage [228].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [228]
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“We have previously shown that exosomal miRNA cargo may depend on intracellular miRNA levels and active/passive transference [39,61,62].”
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MicroRNAs as Regulators of Phagocytosis
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- Authors
- Yin, Z., Han, Z., Hu, T., Zhang, S., Ge, X., Huang, S., Wang, L., Yu, J., Li, W., Wang, Y., li, D., Zhao, J., Wang, Y., Zuo, Y., Li, Y., Kong, X., Chen, F., & Lei, P.
- Affiliations
- Tianjin Medical University General Hospital (CN)
- Corresponding author
- Lei, Ping
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 83
- Pages
- 270-282
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2983415011
- Cited by
- 171
- References
- 6
- Citations by year
- 2026: 17 · 2025: 31 · 2024: 38 · 2023: 36 · 2022: 25 · 2021: 14 · 2020: 9
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-08-01)
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81772060, 81501055)
- Tianjin Municipal Science and Technology Commission Natural Fund Project (18JCQNJC81100, 18ZXDBSY00090, 19JCQNJC10200)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- miR-21-5p, M1 microglia polarization, neuroinflammation, traumatic brain injury, chronic traumatic encephalopathy, microglia-neuron interaction, neurite outgrowth, tau phosphorylation, neuronal apoptosis
- MeSH terms
- Brain Injuries, Traumatic, Animals, Cell Differentiation, Inflammation, Male, Neurons, PC12 Cells, Microglia, Coculture Techniques, MicroRNAs, Mice, Rats, Exosomes
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