SPARC IS A SOURCE OF COPPER-BINDING PEPTIDES THAT STIMULATE ANGIOGENESIS
SPARC IS A SOURCE OF COPPER-BINDING PEPTIDES THAT STIMULATE ANGIOGENESIS
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DOI：
10.1083/jcb.125.4.929
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发表时间：
1994-05-01
影响因子：
7.8
通讯作者：
SAGE, EH
中科院分区：
文献类型：
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作者：
LANE, TF;IRUELAARISPE, ML;SAGE, EH
SPARC 是一种瞬时表达的细胞外基质结合蛋白，可在体外改变细胞形状并调节内皮细胞增殖。在这项研究中，我们证明 SPARC mRNA 和蛋白质是在体内血管生成过程中由内皮细胞合成的，SPARC 和源自蛋白质阳离子区域（氨基酸 113-130）的肽在体外刺激内皮索的形成；此外，这些肽刺激体内血管生成。活性结构域的图谱表明序列 KGHK 负责大部分血管生成活性； His残基的取代降低了效果。我们发现 SPARC 的蛋白水解提供了 KGHK、GHK 和包含这些序列的较长肽的来源。尽管 Cu2+-GHK 复合物已被鉴定为正常人血浆中的有丝分裂原/形态发生素，但我们发现 KGHK 和更长的肽是血管生成的有效刺激剂。 SPARC(113-130) 和 KGHK 能够以高亲和力结合 Cu2+；然而，刺激活性不需要预先与 CU2+ 一起孵育。由于来自 SPARC 第二个阳离子区域 (SPARC(54-73)) 的肽也结合 CU2+ 但对血管生成没有影响，因此血管生成活性似乎是序列特异性的并且独立于结合的 Cu2+。因此，SPARC（一种由内皮细胞在血管重塑过程中表达的基质相关蛋白）的特异性降解会释放出一种或多种生物活性肽，其中含有序列（K）GHK，可以调节体内血管生成。
SPARC is a transiently expressed extracellular matrix-binding protein that alters cell shape and regulates endothelial cell proliferation in vitro. In this study, we show that SPARC mRNA and protein are synthesized by endothelial cells during angiogenesis in vivo, SPARC and peptides derived from a cationic region of the protein (amino acids 113-130) stimulated the formation of endothelial cords in vitro; moreover, these peptides stimulated angiogenesis in vivo. Mapping of the active domain demonstrated that the sequence KGHK was responsible for most of the angiogenic activity; substitution of the His residue decreased the effect. We found that proteolysis of SPARC provided a source of KGHK, GHK, and longer peptides that contained these sequences. Although the Cu2+-GHK complex had been identified as a mitogen/morphogen in normal human plasma, we found KGHK and longer peptides to be potent stimulators of angiogenesis. SPARC(113-130) and KGHK were shown to bind Cu2+ with high affinity; however, previous incubation with CU2+ was not required for the stimulatory activity. Since a peptide from a second cationic region of SPARC (SPARC(54-73)) also bound CU2+ but had no effect on angiogenesis, the angiogenic activity appeared to be sequence specific and independent of bound Cu2+. Thus, specific degradation of SPARC, a matrix-associated protein expressed by endothelial cells during vascular remodeling, releases a bioactive peptide or peptides, containing the sequence (K)GHK, that could regulate angiogenesis in vivo.