Malinda K M, Nomizu M, Chung M, Delgado M, Kuratomi Y, Yamada Y, Kleinman H K, Ponce M L
a Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, NIH, Bethesda, Maryland 20892-4370, USA.
FASEB J. 1999 Jan;13(1):53-62.
Laminin-1 is a basement membrane glycoprotein that promotes several biological activities including cell attachment, tumor metastasis, and angiogenesis. Angiogenesis plays an important role in tissue formation, reproduction, wound healing, and several pathological conditions. In this study, we screened 405 synthetic peptides from the alpha1 and beta1 chains to identify potential sites on laminin-1 active with endothelial cells. Peptides were initially screened by testing both endothelial cell adhesion to peptide-coated wells and tube formation on Matrigel in the presence of soluble peptide. Twenty active peptides were identified in these screens. A secondary screen using the rat aortic ring sprouting assay identified 13 of the 20 peptides that stimulated endothelial sprouting. Several of these active peptides were also found to stimulate human umbilical vein endothelial cell migration in Boyden chamber assays. Differences in the amount of peptide needed for the response and in the resultant morphologies/responses were observed between the peptides in all of the assays. Our results suggest that several active domains on laminin-1 may play important roles in stimulating different steps in angiogenesis.
层粘连蛋白-1是一种基底膜糖蛋白，可促进多种生物活性，包括细胞黏附、肿瘤转移和血管生成。血管生成在组织形成、生殖、伤口愈合以及多种病理状况中发挥着重要作用。在本研究中，我们从α1链和β1链筛选了405种合成肽，以确定层粘连蛋白-1上与内皮细胞有活性的潜在位点。最初通过检测内皮细胞对包被肽的孔的黏附以及在可溶性肽存在下在基质胶上形成管腔来筛选肽。在这些筛选中鉴定出了20种活性肽。使用大鼠主动脉环芽生试验进行的二次筛选在这20种肽中鉴定出13种可刺激内皮芽生的肽。在博伊登室试验中还发现其中几种活性肽可刺激人脐静脉内皮细胞迁移。在所有试验中，各肽之间在产生反应所需的肽量以及由此产生的形态/反应方面均观察到差异。我们的结果表明，层粘连蛋白-1上的几个活性结构域可能在刺激血管生成的不同步骤中发挥重要作用。
