Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes
Abstract Background Spinal cord injury (SCI) is a catastrophic injury that can cause irreversible motor dysfunction with high disability. Exosomes participate in the transport of miRNAs and play an essential role in intercellular communication via transfer of genetic material. However, the miRNAs in...
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doaj-38613806035943af9934d30e2a20ed932020-11-25T03:38:37ZengBMCJournal of Nanobiotechnology1477-31552020-07-0118112010.1186/s12951-020-00665-8Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytesDongdong Jiang0Fangyi Gong1Xuhui Ge2Chengtang Lv3Chenyu Huang4Shuang Feng5Zheng Zhou6Yuluo Rong7Jiaxing Wang8Chengyue Ji9Jian Chen10Wene Zhao11Jin Fan12Wei Liu13Weihua Cai14Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, Yancheng Third People’s HospitalDepartment of Orthopaedics, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Encephalopathy, The Third Affiliated Hospital of Nanjing University of Chinese MedicineDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Analytical & Testing Center, Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopaedics, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background Spinal cord injury (SCI) is a catastrophic injury that can cause irreversible motor dysfunction with high disability. Exosomes participate in the transport of miRNAs and play an essential role in intercellular communication via transfer of genetic material. However, the miRNAs in exosomes which derived from neurons, and the underlying mechanisms by which they contribute to SCI remain unknown. Methods A contusive in vivo SCI model and a series of in vitro experiments were carried out to explore the therapeutic effects of exosomes. Then, a miRNA microarray analysis and rescue experiments were performed to confirm the role of neuron-derived exosomal miRNA in SCI. Western blot, luciferase activity assay, and RNA-ChIP were used to investigate the underlying mechanisms. Results The results indicated that neuron-derived exosomes promoted functional behavioral recovery by suppressing the activation of M1 microglia and A1 astrocytes in vivo and in vitro. A miRNA array showed miR-124-3p to be the most enriched in neuron-derived exosomes. MYH9 was identified as the target downstream gene of miR-124-3p. A series of experiments were used to confirm the miR-124-3p/MYH9 axis. Finally, it was found that PI3K/AKT/NF-κB signaling cascades may be involved in the modulation of microglia by exosomal miR-124-3p. Conclusion A combination of miRNAs and neuron-derived exosomes may be a promising, minimally invasive approach for the treatment of SCI.http://link.springer.com/article/10.1186/s12951-020-00665-8Spinal cord injuryExosomesMicrogliaAstrocytesmiR-124-3p/MYH9 axis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dongdong Jiang Fangyi Gong Xuhui Ge Chengtang Lv Chenyu Huang Shuang Feng Zheng Zhou Yuluo Rong Jiaxing Wang Chengyue Ji Jian Chen Wene Zhao Jin Fan Wei Liu Weihua Cai |
spellingShingle |
Dongdong Jiang Fangyi Gong Xuhui Ge Chengtang Lv Chenyu Huang Shuang Feng Zheng Zhou Yuluo Rong Jiaxing Wang Chengyue Ji Jian Chen Wene Zhao Jin Fan Wei Liu Weihua Cai Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes Journal of Nanobiotechnology Spinal cord injury Exosomes Microglia Astrocytes miR-124-3p/MYH9 axis |
author_facet |
Dongdong Jiang Fangyi Gong Xuhui Ge Chengtang Lv Chenyu Huang Shuang Feng Zheng Zhou Yuluo Rong Jiaxing Wang Chengyue Ji Jian Chen Wene Zhao Jin Fan Wei Liu Weihua Cai |
author_sort |
Dongdong Jiang |
title |
Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes |
title_short |
Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes |
title_full |
Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes |
title_fullStr |
Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes |
title_full_unstemmed |
Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes |
title_sort |
neuron-derived exosomes-transmitted mir-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes |
publisher |
BMC |
series |
Journal of Nanobiotechnology |
issn |
1477-3155 |
publishDate |
2020-07-01 |
description |
Abstract Background Spinal cord injury (SCI) is a catastrophic injury that can cause irreversible motor dysfunction with high disability. Exosomes participate in the transport of miRNAs and play an essential role in intercellular communication via transfer of genetic material. However, the miRNAs in exosomes which derived from neurons, and the underlying mechanisms by which they contribute to SCI remain unknown. Methods A contusive in vivo SCI model and a series of in vitro experiments were carried out to explore the therapeutic effects of exosomes. Then, a miRNA microarray analysis and rescue experiments were performed to confirm the role of neuron-derived exosomal miRNA in SCI. Western blot, luciferase activity assay, and RNA-ChIP were used to investigate the underlying mechanisms. Results The results indicated that neuron-derived exosomes promoted functional behavioral recovery by suppressing the activation of M1 microglia and A1 astrocytes in vivo and in vitro. A miRNA array showed miR-124-3p to be the most enriched in neuron-derived exosomes. MYH9 was identified as the target downstream gene of miR-124-3p. A series of experiments were used to confirm the miR-124-3p/MYH9 axis. Finally, it was found that PI3K/AKT/NF-κB signaling cascades may be involved in the modulation of microglia by exosomal miR-124-3p. Conclusion A combination of miRNAs and neuron-derived exosomes may be a promising, minimally invasive approach for the treatment of SCI. |
topic |
Spinal cord injury Exosomes Microglia Astrocytes miR-124-3p/MYH9 axis |
url |
http://link.springer.com/article/10.1186/s12951-020-00665-8 |
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