...
首页> 外文期刊>Cell biology international. >JNK as a positive regulator of angiogenic potential in endothelial cells.
【24h】

JNK as a positive regulator of angiogenic potential in endothelial cells.

机译:JNK作为内皮细胞中血管生成潜能的正调节剂。

获取原文
获取原文并翻译 | 示例
           

摘要

Angiogenesis (the growth of new capillaries) occurs in adults in response to physiological stimuli such as wound healing and exercise. The mitogen-activated protein kinase c-jun N-terminal kinase (JNK) has a controversial role in the process of angiogenesis, with previous evidence supporting JNK as both a positive and negative regulator of blood vessel growth. The purpose of this study was to clarify the role of JNK in the angiogenesis process. Phosphorylated JNK was observed in cultured endothelial cells, and levels were constant regardless of extracellular matrix composition. Using SP600125, inhibition of JNK attenuated sprout growth in 3D capillary sprout cultures. Inhibition of JNK reduced endothelial cell proliferation and migration in vitro. JNK inhibition and siRNA knockdown of c-jun (a downstream target of JNK) decreased protein levels of the transcription factor Egr-1, a regulator of genes involved in proliferation and migration. Matrix metalloproteinase-2 (MMP-2) production, and activity also, was reduced in sprout cultures treated with SP600125. c-Jun silencing decreased both MMP-2 and membrane type-1 (MT1)-MMP mRNA in endothelial cells, implicating both JNK and c-jun as activators of proteolysis. Taken together, these results provide evidence that JNK and its downstream target c-jun positively regulate angiogenesis via activation of endothelial cell proliferation, migration and proteolysis.
机译:血管生成(新毛细血管的生长)发生在成年人中,是对诸如伤口愈合和运动之类的生理刺激的反应。丝裂原活化的蛋白激酶c-jun N末端激酶(JNK)在血管生成过程中具有争议的作用,以前的证据支持JNK作为血管生长的正负调节剂。这项研究的目的是阐明JNK在血管生成过程中的作用。在培养的内皮细胞中观察到磷酸化的JNK,无论细胞外基质成分如何,其水平都是恒定的。使用SP600125,JNK的抑制作用会减弱3D毛细血管芽培养物中的芽生长。 JNK的抑制作用降低了体外内皮细胞的增殖和迁移。 JNK的抑制和c-jun(JNK的下游靶标)的siRNA敲低降低了转录因子Egr-1(参与增殖和迁移的基因的调节剂)的蛋白质水平。在用SP600125处理的新芽培养物中,基质金属蛋白酶2(MMP-2)的产生和活性也降低了。 c-Jun沉默降低了内皮细胞中MMP-2和膜1型(MT1)-MMP mRNA的表达,暗示JNK和c-jun都是蛋白水解激活剂。综上,这些结果提供了证据,表明JNK及其下游目标c-jun通过激活内皮细胞增殖,迁移和蛋白水解作用来积极调节血管生成。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号