Fascin-1 is Highly Expressed Specifically in Microglia After Spinal Cord Injury and Regulates Microglial Migration.
Fascin-1 is Highly Expressed Specifically in Microglia After Spinal Cord Injury and Regulates Microglial Migration.
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Fascin-1 在脊髓损伤后的小胶质细胞中特异性高度表达，并调节小胶质细胞的迁移。
DOI：
10.3389/fphar.2021.729524
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发表时间：
2021
影响因子：
5.6
通讯作者：
Jing J
中科院分区：
文献类型：
--
作者：
Yu S;Cheng L;Tian D;Li Z;Yao F;Luo Y;Liu Y;Zhu Z;Zheng M;Jing J
最近的研究表明，脊髓损伤（SCI）后，小胶质细胞聚集在星形胶质细胞和纤维化疤痕之间的病变边缘，具有炎症限制和神经保护功能，但小胶质细胞迁移的机制仍不清楚。Fascin-1是一种调节细胞迁移、侵袭和粘附的关键肌动蛋白捆绑蛋白，但其在SCI中的作用尚未见报道。在此，我们发现，在小鼠SCI后7-14天，Fascin-1显著上调，主要分布在病变周围，并特异性表达于CX 3CR 1阳性的小胶质细胞。然而，Fascin-1在GFAP阳性星形胶质细胞、NeuN阳性神经元、NG 2阳性细胞、PDGFRβ阳性细胞或浸润到病变核心的血液来源的Mac 2阳性巨噬细胞中不表达。在通过集落刺激因子1受体（CSF 1 R）抑制剂PLX 5622特异性地耗尽损伤的脊髓中的小胶质细胞后，Fascin-1的表达相应地降低。当小胶质细胞在体外被髓鞘碎片激活时，观察到Fascin-1表达上调，并且小胶质细胞迁移显著增加。使用小干扰RNA（siRNA）抑制Fascin-1表达显著抑制小胶质细胞的迁移，但这种作用可以通过用髓磷脂处理来逆转。小胶质细胞的M1/M2样极化不影响Fascin-1的表达。总之，我们的研究结果表明，Fascin-1在SCI后的小胶质细胞中特异性高表达，并在小胶质细胞的迁移和小胶质细胞瘢痕的形成中发挥重要作用。因此，阐明这一机制将为SCI的治疗提供新的治疗靶点。
Recent research indicates that after spinal cord injury (SCI), microglia accumulate at the borders of lesions between astrocytic and fibrotic scars and perform inflammation-limiting and neuroprotective functions, however, the mechanism of microglial migration remains unclear. Fascin-1 is a key actin-bundling protein that regulates cell migration, invasion and adhesion, but its role during SCI has not been reported. Here, we found that at 7–14 days after SCI in mice, Fascin-1 is significantly upregulated, mainly distributed around the lesion, and specifically expressed in CX3CR1-positive microglia. However, Fascin-1 is not expressed in GFAP-positive astrocytes, NeuN-positive neurons, NG2-positive cells, PDGFRβ-positive cells, or blood-derived Mac2-positive macrophages infiltrating into the lesion core. The expression of Fascin-1 is correspondingly decreased after microglia are specifically depleted in the injured spinal cord by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622. The upregulation of Fascin-1 expression is observed when microglia are activated by myelin debris in vitro, and microglial migration is prominently increased. The inhibition of Fascin-1 expression using small interfering RNA (siRNA) markedly suppresses the migration of microglia, but this effect can be reversed by treatment with myelin. The M1/M2-like polarization of microglia does not affect the expression of Fascin-1. Together, our results suggest that Fascin-1 is highly expressed specifically in microglia after SCI and can play an important role in the migration of microglia and the formation of microglial scars. Hence, the elucidation of this mechanism will provide novel therapeutic targets for the treatment of SCI.
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影响因子：
3.7
作者：
Hashimoto Y;Loftis DW;Adams JC
通讯作者：
Adams JC
影响因子：
5.3
作者：
Greenhalgh, Andrew D.;David, Samuel
通讯作者：
David, Samuel
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG
血浆血红素通过将小胶质细胞从 M1 状态切换到 M2 状态来改善小鼠脊髓损伤
影响因子：
9
作者：
Han D;Yu Z;Liu W;Yin D;Pu Y;Feng J;Yuan Y;Huang A;Cao L;He C
通讯作者：
He C
影响因子：
9.3
作者：
Bogie JF;Stinissen P;Hellings N;Hendriks JJ
通讯作者：
Hendriks JJ