Radha K S, Madhyastha H K, Nakajima Y, Omura S, Maruyama M
Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
Vascul Pharmacol. 2008 Apr-Jun;48(4-6):184-90. doi: 10.1016/j.vph.2008.02.002. Epub 2008 Feb 15.
Urokinase plasminogen activator (uPA) system is important for several biological processes that call for extracellular proteolysis, fibrinolysis, cell migration, proliferation and angiogenesis. The current study highlights the fibrinolytic and wound healing potential of emodin, an anthraquinone, with relevance to the uPA system. Emodin increased the fibrinolytic activity of fibroblast cells in a dose-dependent manner. Zymography linked the activity to increased uPA activity. Subsequent RT-PCR and western analyses demonstrated uPA gene upregulation. Interestingly, PAI-1, the inhibitor of uPA was also upregulated. EMSA showed the upregulation occurred independent of emodin's effect on nuclear factor kappa B (NFkappaB). The effect on uPA system is supposedly via generation of reactive oxygen species (ROS) since cotreatment with ascorbic acid, an anti-oxidant, attenuated the activity. In addition to profibrinolytic potential, emodin also demonstrated wound healing activity in in vitro wound models. Presence of emodin in the medium enhanced the rate of migration of fibroblasts into the wounded region. These in vitro experiments reveal that emodin is a potent profibrinolytic and wound healing agent.
尿激酶型纤溶酶原激活剂（uPA）系统对于多种需要细胞外蛋白水解、纤维蛋白溶解、细胞迁移、增殖和血管生成的生物学过程至关重要。当前的研究突出了大黄素（一种蒽醌）与uPA系统相关的纤维蛋白溶解和伤口愈合潜力。大黄素以剂量依赖性方式增加成纤维细胞的纤维蛋白溶解活性。酶谱分析将该活性与uPA活性增加联系起来。随后的逆转录聚合酶链反应（RT-PCR）和蛋白质印迹分析表明uPA基因上调。有趣的是，uPA的抑制剂纤溶酶原激活物抑制剂-1（PAI-1）也上调。电泳迁移率变动分析（EMSA）表明这种上调独立于大黄素对核因子κB（NFκB）的影响而发生。对uPA系统的影响推测是通过活性氧（ROS）的产生，因为与抗氧化剂抗坏血酸共同处理可减弱该活性。除了促纤维蛋白溶解潜力外，大黄素在体外伤口模型中也表现出伤口愈合活性。培养基中存在大黄素可提高成纤维细胞向伤口区域迁移的速率。这些体外实验表明大黄素是一种有效的促纤维蛋白溶解和伤口愈合剂。
