证据表明VEGF-Ax的益血管功能
Hong Xin1, Cuiling Zhong1, Eric Nudleman1
1University of California, San Diego, 3855 Health Sciences Drive #0819, La Jolla, CA 92093, USA.
Cell
|September 24, 2016
概括
与之前的发现相反,血管内皮生长因子-Ax (VEGF-Ax) 促进血管形成. 这项研究显示,VEGF-Ax刺激内皮细胞生长和血管透性,影响血管生成研究.
科学领域:
- 分子生物学
- 细胞生物学
- 生物化学
背景情况:
- 血管内皮生长因子A (VEGF-A) 异型对血管发育至关重要.
- VEGF信号通路是各种疾病的有效治疗点.
- 替代mRNA拼接产生多个VEGF-A异型,例如VEGF165.
研究的目的:
- 研究VEGF-Ax异型在内皮细胞中的功能作用.
- 为了澄清关于VEGF-Ax的亲血管性或抗血管性作用的相互矛盾的报告.
- 确定VEGF-Ax对内皮细胞增殖,迁移和血管透性的影响.
主要方法:
- 细胞培养内皮细胞
- 对VEGF-Ax对细胞增殖 (甲基生成) 的影响的分析.
- 血管生成和血管透性测试的评估.
- 检测VEGFR-2酸化的西部抹杀.
- 使用neuropilin-1进行VEGF-Ax和VEGF165结合测定.
主要成果:
- VEGF-Ax显著刺激了内皮细胞的线粒生成,血管生成和血管透性.
- 在VEGFR-2中,VEGF-Ax诱导了关键氨酸残留物的酸化.
- 与VEGF165相比,VEGF-Ax的功效有所降低.
- 观察到VEGF-Ax与神经素-1共受体的结合功能受损.
结论:
- 这与之前的研究相矛盾.
- VEGF-Ax和VEGF165的作用差异部分是由于神经皮林-1结合的变化.
- 在涉及血管生成的治疗策略中,VEGF-Ax是一个新的点.
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