Mitola Stefania, Moroni Emanuela, Ravelli Cosetta, Andres German, Belleri Mirella, Presta Marco
Department of Biomedical Sciences and Biotechnology, Unit of General Pathology and Immunology, University of Brescia, Brescia, Italy.
Blood. 2008 Aug 15;112(4):1154-7. doi: 10.1182/blood-2007-09-111450. Epub 2008 May 27.
Recent observations have shown that Drm, a member the Dan family of bone morphogenic protein (BMP) antagonists, induces endothelial cell (EC) sprouting in vitro and angiogenesis in vivo by interacting with signaling EC receptors in a BMP-independent manner. Here, recombinant Drm (rDrm) up-regulates angiopoientin-1 (Ang-1) expression in EC without affecting Ang-2 and Tie-2 receptor expression. Ang-1 up-regulation is mediated by the activation of the transcription factor NF-kappaB. Specific inhibition of Ang-1 activity by anti-Ang-1 antibodies, soluble Tie-2 receptor, or Ang-1 siRNA transfection significantly reduced the rDrm-mediated sprouting of EC in three-dimensional fibrin and type I collagen gels. In addition, Ang-1 antagonists inhibited the angiogenic activity exerted by rDrm in the chick embryo chorioallantoic membrane. Taken together, the data indicate that the proangiogenic activity of Drm is mediated by the activation of an Ang-1-dependent autocrine loop of stimulation in EC.
最近的观察结果表明，Drm是骨形态发生蛋白（BMP）拮抗剂Dan家族的成员，它通过以BMP非依赖的方式与信号内皮细胞（EC）受体相互作用，在体外诱导内皮细胞发芽并在体内诱导血管生成。在这里，重组Drm（rDrm）上调EC中血管生成素-1（Ang-1）的表达，而不影响Ang-2和Tie-2受体的表达。Ang-1的上调是由转录因子NF-κB的激活介导的。抗Ang-1抗体、可溶性Tie-2受体或Ang-1 siRNA转染对Ang-1活性的特异性抑制显著降低了rDrm介导的EC在三维纤维蛋白和I型胶原凝胶中的发芽。此外，Ang-1拮抗剂抑制了rDrm在鸡胚绒毛尿囊膜上发挥的血管生成活性。综上所述，数据表明Drm的促血管生成活性是由EC中Ang-1依赖性自分泌刺激环的激活介导的。
