Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury.
Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury.
复制标题
从活化的星形胶质细胞中包封CCL2的细胞外小泡诱导创伤性脊髓损伤后小胶质细胞活化和神经元凋亡。
DOI：
10.1186/s12974-021-02268-y
复制
发表时间：
2021-09-12
影响因子：
9.3
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Rong Y;Ji C;Wang Z;Ge X;Wang J;Ye W;Tang P;Jiang D;Fan J;Yin G;Liu W;Cai W
脊髓损伤（Spinal cord injury，SCI）是一种严重的创伤性疾病，致残率和死亡率高。脊髓损伤后的分子病理学特征主要涉及炎症反应、小胶质细胞和神经元凋亡、星形胶质细胞异常增殖和胶质瘢痕形成。然而，脊髓损伤后的微环境变化是复杂的，胶质细胞和神经细胞之间的相互作用仍然不清楚。小细胞外囊泡（sEVs）通过在细胞之间转运RNA、蛋白质和生物活性脂质在细胞通讯中发挥关键作用。很少有研究探讨了SCI后星形胶质细胞通过sEVs的细胞间通讯。已知星形胶质细胞释放的炎症信号启动小胶质细胞活化，但其对SCI后神经元的影响仍有待进一步阐明。应用电子显微镜（TEM）、纳米颗粒跟踪分析（NTA）和蛋白质印迹来表征sEV。我们在急性脊髓损伤的实验模型和体外细胞培养中研究了星形胶质细胞活化介导的小胶质细胞活化和神经元凋亡。我们的研究结果表明，脊髓损伤后激活的星形胶质细胞释放CCL 2，通过sEV通路作用于小胶质细胞和神经元细胞，并在结合CCL 2后促进神经元凋亡和小胶质细胞活化。随后，活化的小胶质细胞释放IL-1β，其作用于神经元细胞，从而进一步加剧其凋亡。本研究阐明了SCI后星形胶质细胞通过sEV通路与小胶质细胞和神经元相互作用，丰富了CCL 2在神经炎症和脊髓神经退行性变中的作用机制，为CCL 2作为SCI治疗靶点提供了新的理论依据。在线版本包含补充材料，可通过10.1186/s12974-021-02268-y获得。
Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The molecular pathological features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified. Electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an experimental model of acute spinal cord injury and in cell culture in vitro. Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1β, which acts on neuronal cells, thereby further aggravating their apoptosis. This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theoretical basis of CCL2 as a therapeutic target for SCI. The online version contains supplementary material available at 10.1186/s12974-021-02268-y.
登录
查看更多内容
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
DOI：
10.3233/jad-2012-120598
发表时间：
2012
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Ho L;Zhao W;Dams-O'Connor K;Tang CY;Gordon W;Peskind ER;Yemul S;Haroutunian V;Pasinetti GM
通讯作者：
Pasinetti GM
接枝的人IPS细胞衍生的少突胶质细胞前体细胞有助于脊髓损伤后脱髓鞘轴突的稳健再生。
影响因子：
5.9
作者：
Kawabata S;Takano M;Numasawa-Kuroiwa Y;Itakura G;Kobayashi Y;Nishiyama Y;Sugai K;Nishimura S;Iwai H;Isoda M;Shibata S;Kohyama J;Iwanami A;Toyama Y;Matsumoto M;Nakamura M;Okano H
通讯作者：
Okano H
影响因子：
3.3
作者：
Fan B;Wei Z;Yao X;Shi G;Cheng X;Zhou X;Zhou H;Ning G;Kong X;Feng S
通讯作者：
Feng S
影响因子：
4.8
作者：
Ahuja, Christopher S.;Nori, Satoshi;Fehlings, Michael G.
通讯作者：
Fehlings, Michael G.