Promotion of corneal epithelial wound healing by a tetrapeptide (SSSR) derived from IGF-1
Promotion of corneal epithelial wound healing by a tetrapeptide (SSSR) derived from IGF-1
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DOI：
10.1167/iovs.05-1205
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Nishida, Teruo
中科院分区：
文献类型：
--
作者：
Yamada, Naoyuki;Yanai, Ryoji;Nishida, Teruo
目的.先前的研究表明，衍生自P物质（SP）羧基末端的四肽（FGLM-酰胺）和对应于胰岛素样生长因子（IGF）-1的C结构域的12-残基肽模拟全长分子对角膜上皮伤口愈合的协同作用。为了开发一种有效的治疗持续性角膜上皮缺损的方法，目前的研究是为了研究IGF-1的C结构域内的最小序列，这是与SP或FGLM-酰胺协同作用所必需的。用兔角膜器官培养系统评价IGF-1衍生肽对角膜上皮迁移的影响。一种四肽（SSSR;来源于IGF-1的C结构域的Ser（33）-Ser-Ser-Arg）足以与FGLM-酰胺协同促进体外角膜上皮迁移和体内伤口闭合。SSSR肽的活性是序列特异性的，并且其效力与IGF-1的效力相似。SSSR肽本身也在较高浓度下促进体外角膜上皮迁移。然而，它缺乏IGF-1的促有丝分裂作用和全长分子诱导新血管形成的能力。SSSR序列介导IGF-1与SP对角膜上皮伤口愈合的协同作用。预期SSSR肽的临床应用不会产生与全长IGF-1治疗相关的潜在有害副作用。因此，单独或与FGLM-酰胺组合局部施用SSSR四肽是治疗不愈合上皮伤口的潜在新策略。
PURPOSE. A prior study showed that a tetrapeptide (FGLM-amide) derived from the carboxyl terminus of substance P (SP) and a 12-residue peptide corresponding to the C domain of insulin-like growth factor (IGF)-1 mimic the synergistic effect of the full-length molecules on corneal epithelial wound healing. To develop an effective treatment for persistent corneal epithelial defects, the current study was conducted to investigate the minimal sequence within the C domain of IGF-1 that is required for such synergism with SP or FGLM-amide.METHODS. The effects of IGF-1-derived peptides on corneal epithelial migration were evaluated with a rabbit corneal organ-culture system.RESULTS. A tetrapeptide (SSSR; Ser(33)-Ser-Ser-Arg) derived from the C domain of IGF-1 was sufficient for the synergistic promotion with FGLM-amide both of corneal epithelial migration in vitro and of wound closure in vivo. The activity of the SSSR peptide was sequence specific and its potency was similar to that of IGF-1. The SSSR peptide by itself also promoted corneal epithelial migration in vitro at higher concentrations. It was devoid, however, of both the mitogenic action of IGF-1 and the ability of the full-length molecule to induce neovascularization.CONCLUSIONS. The SSSR sequence mediates the synergistic effect of IGF-1 with SP on corneal epithelial wound healing. Clinical application of the SSSR peptide would be expected to be free of potentially deleterious side effects associated with treatment with full-length IGF-1. Local administration of the SSSR tetrapeptide, alone or in combination with FGLM-amide, is thus a potential new strategy for the treatment of nonhealing epithelial wounds.