Genentech, Inc., South San Francisco, CA 94080, USA.
Mol Biol Cell. 2010 Mar 1;21(5):687-90. doi: 10.1091/mbc.e09-07-0590.
Vascular endothelial growth factor (VEGF, VEGF-A) is a major regulator of physiological and pathological angiogenesis. One feature of VEGF is the existence of multiple isoforms arising from alternative exon splicing. Our initial biochemical and biological studies indicated that such isoforms are uniquely suited to generate angiogenic gradients by virtue of their differential ability to interact with the extracellular matrix (ECM). Although ECM-bound VEGF was bioactive, processing by physiologically relevant proteases such as plasmin was identified as a key mechanism to convert ECM-bound VEGF into freely diffusible forms. This retrospective article examines the early studies and also emphasizes the subsequent progress in our understanding of these processes in health and disease.
血管内皮生长因子（VEGF，VEGF-A）是生理和病理血管生成的主要调节剂。VEGF 的一个特征是存在多种由选择性外显子剪接产生的同工型。我们最初的生化和生物学研究表明，这些同工型通过其与细胞外基质（ECM）相互作用的差异能力，非常适合产生血管生成梯度。尽管 ECM 结合的 VEGF 具有生物活性，但生理相关蛋白酶（如纤溶酶）的处理被确定为将 ECM 结合的 VEGF 转化为自由扩散形式的关键机制。本文回顾了早期的研究，并强调了随后在我们对这些在健康和疾病中过程的理解方面的进展。
