Vitronectin Regulates the Fibrinolytic System during the Repair of Cerebral Cortex in Stab-Wounded Mice
Vitronectin Regulates the Fibrinolytic System during the Repair of Cerebral Cortex in Stab-Wounded Mice
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DOI：
10.1089/neu.2017.5008
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发表时间：
2017-11-15
影响因子：
4.2
通讯作者：
Miyamoto, Yasunori
中科院分区：
文献类型：
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作者：
Hashimoto, Kei;Ikeda, Natsumi;Miyamoto, Yasunori
玻璃体连接蛋白（VN）是一种血清蛋白，已知参与血液凝固、纤维蛋白溶解和细胞迁移的调节。有研究认为，VN对纤维蛋白溶解的调节促进了脑损伤（如创伤性损伤和蛛网膜下腔出血）后血脑屏障（BBB）的恢复。然而，VN对损伤脑纤维蛋白溶解的影响尚不清楚。我们检测了VN对VN敲除（KO）小鼠刺伤大脑皮层纤维蛋白溶解系统的影响。首先，通过血清免疫球蛋白G （IgG）外渗来评估损伤区域血脑屏障破裂后的出血和恢复情况。与野生型小鼠相比，VN- ko小鼠在刺伤后3-7天（D3-7）皮层IgG外渗水平升高，说明VN缺乏抑制了血脑屏障破坏后的恢复。VN缺乏减少D1-3的纤维蛋白纤维沉积，表明VN缺乏使纤维蛋白生成和纤维蛋白溶解之间的平衡向纤维蛋白溶解倾斜。接下来，我们分析了VN缺乏对刺伤皮质纤维蛋白溶解因子的影响。VN缺乏损害了D3-5处纤溶酶原激活物抑制剂-1（一种纤溶系统抑制剂）的活性。此外，VN缺乏上调了组织型纤溶酶原激活物和尿激酶型纤溶酶原激活物的mRNA和蛋白表达水平。这些结果表明，VN有助于调节损伤脑血脑屏障破坏后的纤维蛋白溶解系统和恢复。
Vitronectin (VN), one of the serum proteins, is known to be involved in the regulation of blood coagulation, fibrinolysis, and cell migration. It has been proposed that the regulation of fibrinolysis by VN promotes the blood-brain barrier (BBB) recovery from brain injuries such as traumatic injury and subarachnoid hemorrhage. The effects of VN on fibrinolysis in the injured brain remain unclear, however. We examined the effects of VN on the fibrinolytic system in the stab-wounded cerebral cortex of VN-knockout (KO) mice. First, hemorrhage and recovery from BBB breakdown in the wounded regions were assessed by serum immunoglobulin G (IgG) extravasation. The level of IgG extravasation increased 3-7 days after the stab wound (D3-7) in the cortex of VN-KO mice, compared with that in wild type mice, indicating that VN deficiency inhibited the recovery from BBB breakdown. The VN deficiency decreased fibrin fiber deposition at D1-3, suggesting that VN deficiency tilts the balance between fibrinogenesis and fibrinolysis toward fibrinolysis. Next, the effects of VN deficiency on the fibrinolytic factors were analyzed in the stab-wounded cortex. The VN deficiency impaired the activity of plasminogen activator inhibitor-1, an inhibitor of the fibrinolytic system, at D3-5. Further, VN deficiency up-regulated the mRNA and protein expression levels of tissue-type plasminogen activator, and urokinase-type plasminogen activator. These results demonstrate that VN contributes to the regulation of the fibrinolytic system and recovery from BBB breakdown in the wounded brain.