Sensitizing effect of substance P on corneal epithelial migration induced by IGF-1, fibronectin, or interleukin-6.
Sensitizing effect of substance P on corneal epithelial migration induced by IGF-1, fibronectin, or interleukin-6.
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DOI：
10.1167/iovs.04-0775
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发表时间：
2005-03
影响因子：
4.4
通讯作者：
Naoyuki Yamada;R. Yanai;M. Inui;T. Nishida
中科院分区：
文献类型：
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作者：
Naoyuki Yamada;R. Yanai;M. Inui;T. Nishida
P物质（SP）存在于角膜上皮的感觉神经纤维中。各种生物制剂，包括表皮生长因子、纤连蛋白、白细胞介素-6以及SP和胰岛素样生长因子（IGF）-1的组合，促进角膜上皮伤口的愈合。研究了SP在角膜上皮迁移中的作用。方法采用器官培养的兔角膜，观察不同药物对角膜上皮迁移的影响。结果SP衍生的四肽，FGLM-酰胺，不仅通过IGF-1衍生的肽（C-结构域肽），而且通过纤连蛋白或白细胞介素-6诱导角膜上皮迁移的剂量-反应关系转移到较低的浓度。SP的这种作用可被磷脂酶C抑制剂、肌醇1，4，5-三磷酸受体介导的Ca（2+）从细胞内储存释放抑制剂以及Ca（2+）和钙调素依赖性蛋白激酶II（CaM-PK II）抑制剂所阻止。结论：这些结果表明，SP，作用于神经激肽1型受体，作为一个重要的调制器的角膜上皮伤口愈合激活CaM-PK II上皮细胞，从而使他们敏感的诱导迁移的各种生物制剂。它们还为角膜伤口治疗的新策略提供了重要的见解。
PURPOSE Substance P (SP) is present in the sensory nerve fibers of the corneal epithelium. Various biological agents, including epidermal growth factor, fibronectin, interleukin-6, and the combination of SP and insulin-like growth factor (IGF)-1, promote the healing of corneal epithelial wounds. The role of SP in corneal epithelial migration was examined. METHODS The effects of various agents on corneal epithelial migration were investigated with the rabbit cornea in an organ culture system. RESULTS An SP-derived tetrapeptide, FGLM-amide, shifted the dose-response relations for the induction of corneal epithelial migration not only by an IGF-1-derived peptide (C-domain peptide) but also by fibronectin or interleukin-6 to lower concentrations. This action of SP was prevented by inhibitors of phospholipase C, of the inositol 1,4,5-trisphosphate receptor-mediated release of Ca(2+) from intracellular stores, and of Ca(2+)- and calmodulin-dependent protein kinase II (CaM-PK II). CONCLUSIONS These results indicate that SP, acting at the neurokinin type 1 receptor, functions as an important modulator of corneal epithelial wound healing by activating CaM-PK II in epithelial cells and thereby sensitizing them to the induction of migration by various biological agents. They also provide important insight into a new strategy for the treatment of corneal wounds.