Role of the C domain of IGFs in synergistic promotion, with a substance P-derived peptide, of rabbit corneal epithelial wound healing.
Role of the C domain of IGFs in synergistic promotion, with a substance P-derived peptide, of rabbit corneal epithelial wound healing.
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DOI：
10.1167/iovs.03-0626
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发表时间：
2004-04
影响因子：
4.4
通讯作者：
Naoyuki Yamada;R. Yanai;Masatsugu Nakamura;M. Inui;T. Nishida
中科院分区：
文献类型：
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作者：
Naoyuki Yamada;R. Yanai;Masatsugu Nakamura;M. Inui;T. Nishida
目的：胰岛素样生长因子（IGFs）和P物质（SP）或SP衍生肽（fglm -酰胺）在体外和体内协同促进角膜上皮伤口愈合。通过测定IGFs的相关功能域，进一步研究了这种协同作用的机制和这些药物的临床潜力。方法在兔角膜器官培养系统中观察igf衍生肽对角膜上皮细胞迁移的影响。用正庚醇清创后兔体内角膜上皮伤口愈合情况也进行了评估。结果在fglm -酰胺存在的情况下，IGF-1或-2 C结构域对应的肽在体外显著促进角膜上皮的迁移，其程度与全长分子相似。相反，与这些生长因子D结构域对应的肽则没有这种作用。IGF-1 C区丝氨酸-34突变为丙氨酸，使其与fglm -酰胺对角膜上皮迁移的协同作用失效。无论fglm -酰胺是否存在，胰岛素原的C肽都不影响角膜上皮的迁移。同时含有IGF-1 c结构域肽和fglm -酰胺的滴眼液在体内显著促进角膜上皮伤口愈合。结论：IGF-1或igf -2的C结构域对这些生长因子与SP在角膜上皮迁移中的协同作用至关重要，但其生物学功能尚未被发现。
PURPOSE Insulin-like growth factors (IGFs) and either substance P (SP) or an SP-derived peptide (FGLM-amide) synergistically facilitate corneal epithelial wound healing in vitro and in vivo. The mechanism of this synergism and the clinical potential of these agents were further investigated by determination of the relevant functional domain of IGFs. METHODS The effects of IGF-derived peptides on corneal epithelial cell migration were evaluated with the rabbit cornea in an organ culture system. Corneal epithelial wound closure in vivo was also evaluated in rabbits after epithelial debridement with n-heptanol. RESULTS In the presence of FGLM-amide, peptides corresponding to the C domain of IGF-1 or -2 significantly promoted corneal epithelial migration in vitro to an extent similar to that apparent with the full-length molecules. In contrast, peptides corresponding to the D domain of these growth factors had no such effect. Mutation of serine-34 in the C domain of IGF-1 to alanine abolished the synergistic effect with FGLM-amide on corneal epithelial migration. The C peptide of proinsulin did not affect corneal epithelial migration in the absence or presence of FGLM-amide. The administration of eye drops containing both the C-domain peptide of IGF-1 and FGLM-amide significantly promoted corneal epithelial wound closure in vivo. CONCLUSIONS The C domain of IGF-1 or -2, for which no biological function has previously been identified, is essential for the synergistic effect of these growth factors with SP on corneal epithelial migration.