Grant D S, Kleinman H K, Goldberg I D, Bhargava M M, Nickoloff B J, Kinsella J L, Polverini P, Rosen E M
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1937-41. doi: 10.1073/pnas.90.5.1937.
Scatter factor (also known as hepatocyte growth factor) is a glycoprotein secreted by stromal cells that stimulates cell motility and proliferation. In vitro, scatter factor stimulates vascular endothelial cell migration, proliferation, and organization into capillary-like tubes. Using two different in vivo assays, we showed that physiologic quantities of purified native mouse scatter factor and recombinant human hepatocyte growth factor induce angiogenesis (the formation of new blood vessels). The angiogenic activity was blocked by specific anti-scatter factor antibodies. Scatter factor induced cultured microvascular endothelial cells to accumulate and secrete significantly increased quantities of urokinase, an enzyme associated with development of an invasive endothelial phenotype during angiogenesis. We further showed that immunoreactive scatter factor is present surrounding sites of blood vessel formation in psoriatic skin. These findings suggest that scatter factor may act as a paracrine mediator in pathologic angiogenesis associated with human inflammatory disease.
分散因子(也称为肝细胞生长因子)是一种由基质细胞分泌的糖蛋白,可刺激细胞运动和增殖。在体外,分散因子可刺激血管内皮细胞迁移、增殖并组织形成毛细血管样管。通过两种不同的体内试验,我们发现生理量的纯化天然小鼠分散因子和重组人肝细胞生长因子可诱导血管生成(新血管的形成)。血管生成活性被特异性抗分散因子抗体阻断。分散因子诱导培养的微血管内皮细胞积聚并分泌大量增加的尿激酶,尿激酶是一种与血管生成过程中侵袭性内皮表型发展相关的酶。我们进一步表明,免疫反应性分散因子存在于银屑病皮肤血管形成部位周围。这些发现表明,分散因子可能在与人类炎症性疾病相关的病理性血管生成中作为旁分泌介质发挥作用。