Faury G, Usson Y, Robert-Nicoud M, Robert L, Verdetti J
Groupe d'Electrophysiologie Moleculaire-Lab Bioenergetique Fondamentale et Appliquee, Institut Albert Bonniot, Universite J. Fourier, BP 53 X, F38041 Grenoble, France.
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2967-72. doi: 10.1073/pnas.95.6.2967.
The extracellular matrix protein "elastin" is the major component of elastic fibers present in the arterial wall. Physiological degradation of elastic fibers, enhanced in vascular pathologies, leads to the presence of circulating elastin peptides (EP). EP have been demonstrated to influence cell migration and proliferation. EP also induce, at circulating pathophysiological concentrations (and not below), an endothelium- and NO- dependent vasorelaxation mediated by the 67-kDa subunit of the elastin-laminin receptor. Here, by using the techniques of patch-clamp, spectrofluorimetry and confocal microscopy, we demonstrate that circulating concentrations of EP activate low specificity calcium channels on human umbilical venous endothelial cells, resulting in increase in cytoplasmic and nuclear free calcium concentrations. This action is independent of phosphoinositide metabolism. Furthermore, these effects are inhibited by lactose, an antagonist of the elastin-laminin receptor, and by cytochalasin D, an actin microfilament depolymerizer. These observations suggest that EP-induced signal transduction is mediated by the elastin-laminin receptor via coupling of cytoskeletal actin microfilaments to membrane channels and to the nucleus. Because vascular remodeling and carcinogenesis are accompanied by extracellular matrix modifications involving elastin, the processes here described could play a role in the elastin-laminin receptor-mediated cellular migration, differentiation, proliferation, as in atherogenesis, and metastasis formation.
细胞外基质蛋白“弹性蛋白”是动脉壁中弹性纤维的主要成分。弹性纤维的生理降解在血管病变中会增强，导致循环弹性蛋白肽（EP）的出现。已证明EP会影响细胞迁移和增殖。EP还会在循环病理生理浓度（而非低于该浓度）时，诱导由弹性蛋白-层粘连蛋白受体的67-kDa亚基介导的内皮依赖性和一氧化氮依赖性血管舒张。在此，我们通过使用膜片钳、荧光光谱法和共聚焦显微镜技术证明，循环浓度的EP会激活人脐静脉内皮细胞上的低特异性钙通道，导致细胞质和细胞核内游离钙浓度增加。这一作用与磷酸肌醇代谢无关。此外，这些效应会被弹性蛋白-层粘连蛋白受体的拮抗剂乳糖以及肌动蛋白微丝解聚剂细胞松弛素D所抑制。这些观察结果表明，EP诱导的信号转导是由弹性蛋白-层粘连蛋白受体通过细胞骨架肌动蛋白微丝与膜通道及细胞核的偶联介导的。由于血管重塑和致癌作用伴随着涉及弹性蛋白的细胞外基质修饰，此处描述的过程可能在弹性蛋白-层粘连蛋白受体介导的细胞迁移、分化、增殖中发挥作用，如在动脉粥样硬化形成和转移形成过程中。
