Cameron J D, Skubitz A P, Furcht L T
Department of Ophthalmology, University of Minnesota, Minneapolis 55455.
Invest Ophthalmol Vis Sci. 1991 Sep;32(10):2766-73.
Type IV collagen, a 500-kilodalton (alpha 1)2(alpha 2)1 heterotrimer with noncollagenous domains (NC1) is the major molecule in most basement membranes in the body. In addition to its structural role as scaffolding, type IV collagen is involved in promoting adhesion and migration of various cell types in vitro, including rabbit corneal epithelial cells. This study assessed the effect of purified proteolytic fragments of type IV collagen and selected synthetic peptides derived from the alpha 1 and alpha 2 chains that are related to the adhesion and directed migration of dissociated primary cultured rabbit epithelial cells. Two homologous peptides (HEP-1 and HEP-2) derived from alpha 1 and alpha 2 NC1 regions were found to promote epithelial cell adhesion. A peptide (HEP-3) derived from an interruption of the triple helix of type IV collagen was effective in promoting corneal epithelial cell migration in both chemotaxis and haptotaxis assays. The helical fragment of type IV collagen promoted both directed migration and ample adhesion, indicating that there may be at least another moiety in the helical region responsible for cell adhesion. The results with these peptides revealed to some extent how corneal epithelial cells react at the molecular level with type IV collagen. They could serve as the basis for therapeutic agents to modify corneal epithelial behavior in situations of perturbed wound healing.
IV型胶原蛋白是一种500千道尔顿的(α1)2(α2)1异源三聚体,带有非胶原蛋白结构域(NC1),是人体大多数基底膜中的主要分子。除了作为支架的结构作用外,IV型胶原蛋白还参与促进多种细胞类型在体外的黏附和迁移,包括兔角膜上皮细胞。本研究评估了IV型胶原蛋白的纯化蛋白水解片段以及从α1和α2链衍生的选定合成肽对解离的原代培养兔上皮细胞黏附和定向迁移的影响。发现从α1和α2 NC1区域衍生的两种同源肽(HEP-1和HEP-2)可促进上皮细胞黏附。一种从IV型胶原蛋白三螺旋中断处衍生的肽(HEP-3)在趋化性和趋触性试验中均能有效促进角膜上皮细胞迁移。IV型胶原蛋白的螺旋片段促进了定向迁移和充分黏附,表明螺旋区域可能至少还有另一个负责细胞黏附的部分。这些肽的研究结果在一定程度上揭示了角膜上皮细胞在分子水平上与IV型胶原蛋白的反应方式。它们可作为治疗剂的基础,用于在伤口愈合受干扰的情况下改变角膜上皮行为。