Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Surgery. 2012 Feb;151(2):296-305. doi: 10.1016/j.surg.2011.07.013. Epub 2011 Sep 3.
Del1 is a secreted protein that is expressed in the endothelium during development and can stimulate angiogenesis through integrin binding and signaling. We were interested in the specific effects of del1 on endothelial cell biology to gain insight into its biologic role during angiogenesis.
Primary endothelial cells were treated with a variety of inducers of apoptosis and anoikis followed by assays for numbers of apoptotic cells, and harvest of total protein for immunoblot analysis.
Del1 prevented endothelial cell apoptosis in response to TNFα/IFNγ, etoposide, and anoikis, but had no effect on proliferation. The anti-apoptotic effect was mediated specifically through binding of integrin αvβ3 by the RGD motif. FAK/ERK and Akt signaling were both necessary to mediate the anti-apoptotic effect of Del1 with the exception of anoikis, which required only Akt activation.
Del1 has been previously shown to promote vascular smooth muscle cell adhesion, migration, and proliferation. We demonstrate here that Del1 prevented apoptosis of endothelial cells in cell culture through integrin binding without any effect on proliferation.
Del1 是一种分泌蛋白，在发育过程中在内皮细胞中表达，通过整合素结合和信号转导刺激血管生成。我们对 del1 对内皮细胞生物学的具体影响感兴趣，以深入了解其在血管生成过程中的生物学作用。
用各种诱导细胞凋亡和失巢凋亡的诱导剂处理原代内皮细胞，然后检测凋亡细胞的数量，并提取总蛋白进行免疫印迹分析。
Del1 可防止 TNFα/IFNγ、依托泊苷和失巢凋亡引起的内皮细胞凋亡，但对增殖没有影响。抗凋亡作用是通过整合素 αvβ3 的 RGD 基序特异性结合介导的。FAK/ERK 和 Akt 信号通路都需要介导 Del1 的抗凋亡作用，但失巢凋亡除外，失巢凋亡只需要 Akt 的激活。
Del1 先前已被证明可促进血管平滑肌细胞的黏附、迁移和增殖。我们在此证明，Del1 通过整合素结合防止细胞培养中的内皮细胞凋亡，而对增殖没有任何影响。
