Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood-Spinal Cord Barrier and Functional Recovery
Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood-Spinal Cord Barrier and Functional Recovery
复制标题
bFGF 对 Caveolin-1 和连接蛋白的调节有助于血脊髓屏障的完整性和功能恢复
DOI：
10.1007/s13311-016-0437-3
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发表时间：
2016-10-01
影响因子：
5.7
通讯作者：
Zhang, Hong-Yu
中科院分区：
文献类型：
--
作者：
Ye, Li-Bing;Yu, Xi-Chong;Zhang, Hong-Yu
血脊髓屏障(BSCB)在脊髓损伤(SCI)的修复中起着重要作用，而小窝蛋白-1对屏障的完整性和通透性是必不可少的。碱性成纤维细胞生长因子(碱性成纤维细胞生长因子)是一种重要的神经保护蛋白，对神经细胞的存活起重要作用。本研究旨在探讨碱性成纤维细胞生长因子是否有利于连接蛋白的维持和BSCB的完整性，以确定其与小窝蛋白-1调控的关系。伊文思蓝染色和异硫氰酸荧光素-葡聚糖外渗法检测BSCB的完整性，检测连接蛋白和基质金属蛋白酶，评价运动功能恢复情况。结果表明，碱性成纤维细胞生长因子治疗可促进脊髓挫伤模型大鼠骨髓间充质干细胞的恢复和功能运动的恢复，降低基质金属蛋白酶-9的表达和活性，增加小窝蛋白-1和连接蛋白的表达，包括occludin、claudin-5、p120-catenin和β-catenin。在脑微血管内皮细胞中，碱性成纤维细胞生长因子可使微血管内皮细胞连接蛋白水平升高，小窝蛋白-1小干扰RNA可阻断碱性成纤维细胞生长因子受体1在缺氧缺糖条件下的保护作用，成纤维细胞生长因子受体1的表达及与小窝蛋白-1的共定位显著降低，且这种作用不能被碱性成纤维细胞生长因子1逆转。这些发现为碱性成纤维细胞生长因子对BSCB和脊髓损伤恢复的有益作用，特别是对小窝蛋白-1的调节提供了一个新的机制。
The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and beta-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1.