Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway
Spinal cord injury (SCI) is a catastrophic event mainly involving neuronal apoptosis and axonal disruption, and it causes severe motor and sensory deficits. Due to the complicated pathological process of SCI, there is currently still a lack of effective treatment for SCI. Microglia, a type of immune...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.783017/full |
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| author | Chengjun Li Chengjun Li Chengjun Li Tian Qin Tian Qin Tian Qin Yudong Liu Yudong Liu Yudong Liu Haicheng Wen Haicheng Wen Haicheng Wen Jinyun Zhao Jinyun Zhao Jinyun Zhao Zixiang Luo Zixiang Luo Zixiang Luo Wei Peng Wei Peng Wei Peng Hongbin Lu Hongbin Lu Chunyue Duan Chunyue Duan Chunyue Duan Yong Cao Yong Cao Yong Cao Jianzhong Hu Jianzhong Hu Jianzhong Hu |
| author_facet | Chengjun Li Chengjun Li Chengjun Li Tian Qin Tian Qin Tian Qin Yudong Liu Yudong Liu Yudong Liu Haicheng Wen Haicheng Wen Haicheng Wen Jinyun Zhao Jinyun Zhao Jinyun Zhao Zixiang Luo Zixiang Luo Zixiang Luo Wei Peng Wei Peng Wei Peng Hongbin Lu Hongbin Lu Chunyue Duan Chunyue Duan Chunyue Duan Yong Cao Yong Cao Yong Cao Jianzhong Hu Jianzhong Hu Jianzhong Hu |
| author_sort | Chengjun Li |
| collection | DOAJ |
| description | Spinal cord injury (SCI) is a catastrophic event mainly involving neuronal apoptosis and axonal disruption, and it causes severe motor and sensory deficits. Due to the complicated pathological process of SCI, there is currently still a lack of effective treatment for SCI. Microglia, a type of immune cell residing in the central nervous system (CNS), need to respond to various stimuli to protect neuronal cells from death. It was also reported that microRNAs (miRNAs) had been identified in microglia-derived exosomes that can be taken up by neurons. However, the kinds of miRNAs in exosome cargo derived from microglia and the underlying mechanisms by which they contribute to neuroprotection after SCI remain unknown. In the present study, a contusive SCI mouse model and in vitro experiments were applied to explore the therapeutic effects of microglia-derived exosomes on neuronal apoptosis, axonal regrowth, and functional recovery after SCI. Then, miRNA analysis, rescue experiments, and luciferase activity assays for target genes were performed to confirm the role and underlying mechanism of microglia-derived exosomal miRNAs in SCI. We revealed that microglia-derived exosomes could promote neurological functional recovery by suppressing neuronal apoptosis and promoting axonal regrowth both in vivo and in vitro. MicroRNA-151-3p is abundant in microglia-derived exosomes and is necessary for mediating the neuroprotective effect of microglia-derived exosomes for SCI repair. Luciferase activity assays reported that P53 was the target gene for miR-151-3p and that p53/p21/CDK1 signaling cascades may be involved in the modulation of neuronal apoptosis and axonal regrowth by microglia-derived exosomal microRNA-151-3p. In conclusion, our data demonstrated that microglia-derived exosomes (microglia-Exos) might be a promising, cell-free approach for the treatment of SCI. MicroRNA-151-3p is the key molecule in microglia-derived exosomes that mediates the neuroprotective effects of SCI treatments. |
| first_indexed | 2024-04-11T15:39:00Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-11T15:39:00Z |
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| spelling | doaj.art-469493595f3447ffb4ddda5c74e84b232022-12-22T04:15:53ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.783017783017Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling PathwayChengjun Li0Chengjun Li1Chengjun Li2Tian Qin3Tian Qin4Tian Qin5Yudong Liu6Yudong Liu7Yudong Liu8Haicheng Wen9Haicheng Wen10Haicheng Wen11Jinyun Zhao12Jinyun Zhao13Jinyun Zhao14Zixiang Luo15Zixiang Luo16Zixiang Luo17Wei Peng18Wei Peng19Wei Peng20Hongbin Lu21Hongbin Lu22Chunyue Duan23Chunyue Duan24Chunyue Duan25Yong Cao26Yong Cao27Yong Cao28Jianzhong Hu29Jianzhong Hu30Jianzhong Hu31Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Sports Medicine, Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaKey Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, ChinaSpinal cord injury (SCI) is a catastrophic event mainly involving neuronal apoptosis and axonal disruption, and it causes severe motor and sensory deficits. Due to the complicated pathological process of SCI, there is currently still a lack of effective treatment for SCI. Microglia, a type of immune cell residing in the central nervous system (CNS), need to respond to various stimuli to protect neuronal cells from death. It was also reported that microRNAs (miRNAs) had been identified in microglia-derived exosomes that can be taken up by neurons. However, the kinds of miRNAs in exosome cargo derived from microglia and the underlying mechanisms by which they contribute to neuroprotection after SCI remain unknown. In the present study, a contusive SCI mouse model and in vitro experiments were applied to explore the therapeutic effects of microglia-derived exosomes on neuronal apoptosis, axonal regrowth, and functional recovery after SCI. Then, miRNA analysis, rescue experiments, and luciferase activity assays for target genes were performed to confirm the role and underlying mechanism of microglia-derived exosomal miRNAs in SCI. We revealed that microglia-derived exosomes could promote neurological functional recovery by suppressing neuronal apoptosis and promoting axonal regrowth both in vivo and in vitro. MicroRNA-151-3p is abundant in microglia-derived exosomes and is necessary for mediating the neuroprotective effect of microglia-derived exosomes for SCI repair. Luciferase activity assays reported that P53 was the target gene for miR-151-3p and that p53/p21/CDK1 signaling cascades may be involved in the modulation of neuronal apoptosis and axonal regrowth by microglia-derived exosomal microRNA-151-3p. In conclusion, our data demonstrated that microglia-derived exosomes (microglia-Exos) might be a promising, cell-free approach for the treatment of SCI. MicroRNA-151-3p is the key molecule in microglia-derived exosomes that mediates the neuroprotective effects of SCI treatments.https://www.frontiersin.org/articles/10.3389/fcell.2021.783017/fullmicrogliaspinal cord injuryneuronal apoptosisexosomesmiR-151-3p |
| spellingShingle | Chengjun Li Chengjun Li Chengjun Li Tian Qin Tian Qin Tian Qin Yudong Liu Yudong Liu Yudong Liu Haicheng Wen Haicheng Wen Haicheng Wen Jinyun Zhao Jinyun Zhao Jinyun Zhao Zixiang Luo Zixiang Luo Zixiang Luo Wei Peng Wei Peng Wei Peng Hongbin Lu Hongbin Lu Chunyue Duan Chunyue Duan Chunyue Duan Yong Cao Yong Cao Yong Cao Jianzhong Hu Jianzhong Hu Jianzhong Hu Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway Frontiers in Cell and Developmental Biology microglia spinal cord injury neuronal apoptosis exosomes miR-151-3p |
| title | Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway |
| title_full | Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway |
| title_fullStr | Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway |
| title_full_unstemmed | Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway |
| title_short | Microglia-Derived Exosomal microRNA-151-3p Enhances Functional Healing After Spinal Cord Injury by Attenuating Neuronal Apoptosis via Regulating the p53/p21/CDK1 Signaling Pathway |
| title_sort | microglia derived exosomal microrna 151 3p enhances functional healing after spinal cord injury by attenuating neuronal apoptosis via regulating the p53 p21 cdk1 signaling pathway |
| topic | microglia spinal cord injury neuronal apoptosis exosomes miR-151-3p |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.783017/full |
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