GIT1 protects traumatically injured spinal cord by prompting microvascular endothelial cells to clear myelin debris.
GIT1 protects traumatically injured spinal cord by prompting microvascular endothelial cells to clear myelin debris.
复制标题
DOI：
10.18632/aging.202560
复制
发表时间：
2021-02-17
期刊：
影响因子：
--
通讯作者：
Yin G
中科院分区：
文献类型：
--
作者：
Wan B;Li C;Wang M;Kong F;Ding Q;Zhang C;Liu H;Qian D;Deng W;Chen J;Tang P;Wang Q;Zhao S;Zhou Z;Xu T;Huang Y;Gu J;Fan J;Yin G
髓鞘碎片的清除是脊髓损伤（SCI）后功能恢复的关键步骤。与吞噬细胞一样，微血管内皮细胞（MEC）在一周内参与损伤部位的髓鞘碎片清除。我们的小组已经证实，G蛋白偶联受体激酶2相互作用蛋白1（GIT 1）是必不可少的自噬和血管生成，这两者都是密切相关的摄取和髓鞘碎片的MEC降解。在此，我们分析了GIT 1在SCI后髓鞘碎片清除中的表现和机制。建立脊髓挫伤模型，用髓鞘碎片处理体外培养的MEC。在GIT 1 WT小鼠中观察到创伤性SCI的恢复比GIT 1 KO小鼠更好。更重要的是，我们发现GIT1促进MEC清除髓鞘碎片，并进一步增强体内和体外MEC的血管生成。从机制上讲，GIT 1介导的自噬有助于MEC清除髓鞘碎片。在这项研究中，我们证明了GIT1可以通过自噬促进MEC清除髓鞘碎片，并通过上调VEGF进一步刺激MEC血管生成。我们的研究结果表明，GITI可以作为一个有前途的目标，加速髓鞘碎片的清除和改善SCI的恢复。
The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). As phagocytes do, microvascular endothelial cells (MECs) participate in myelin debris clearance at the injury site within one week. Our group has verified that G protein-coupled receptor kinase 2 interacting protein-1 (GIT1) is essential in autophagy and angiogenesis, both of which are tightly related to the uptake and degradation of myelin debris by MECs. Here, we analyzed the performance and mechanism of GIT1 in myelin debris clearance after SCI. The SCI contusion model was established and in vitro MECs were treated with myelin debris. Better recovery from traumatic SCI was observed in the GIT1 WT mice than in the GIT1 KO mice. More importantly, we found that GIT1 prompted MECs to clear myelin debris and further enhanced MECs angiogenesis in vivo and in vitro. Mechanistically, GIT1-mediated autophagy contributed to the clearance of myelin debris by MECs. In this study, we demonstrated that GIT1 may prompt MECs to clear myelin debris via autophagy and further stimulate MECs angiogenesis via upregulating VEGF. Our results indicate that GITI may serve as a promising target for accelerating myelin debris clearance and improving SCI recovery.