Ofuji K, Nakamura M, Nishida T
Department of Ophthalmology, Yamaguchi University School of Medicine, Ube City, Japan.
Jpn J Ophthalmol. 2000 Jan-Feb;44(1):1-8. doi: 10.1016/s0021-5155(99)00168-9.
In a previous report we showed that substance P (SP) and insulin-like growth factor-1 (IGF-1) or epidermal growth factor (EGF) synergistically stimulate corneal epithelial migration. In this study, we used an organ culture system of rabbit cornea to identify which signal transduction system affects corneal epithelial migration.
Rabbit corneal blocks were cultured in TC-199 culture medium containing various reagents for 24 hours. After the end of cultivation, the length of the path of epithelial migration was measured.
Acting alone, protein kinase C (PKC) inhibitors, calphostin C and H-7, each reduced the length of epithelial migration. Tyrosine kinase (TK) inhibitors, genistein and herbimycin A, also acted individually to inhibit epithelial migration. The synergistic stimulatory effects of SP and IGF-1 on corneal epithelial migration were eliminated when PKC inhibitors or TK inhibitors were added. The synergistic effect of SP and EGF was eliminated by TK inhibitors, but only partly suppressed by PKC inhibitors.
These results suggest that the synergistic effect of SP and EGF might require a TK pathway, and that the synergistic effect of SP and IGF-1 might require both PKC and TK pathways.
在之前的一份报告中，我们表明P物质（SP）与胰岛素样生长因子-1（IGF-1）或表皮生长因子（EGF）协同刺激角膜上皮迁移。在本研究中，我们使用兔角膜器官培养系统来确定哪种信号转导系统影响角膜上皮迁移。
将兔角膜块在含有各种试剂的TC-199培养基中培养24小时。培养结束后，测量上皮迁移路径的长度。
单独作用时，蛋白激酶C（PKC）抑制剂钙泊三醇C和H-7均缩短了上皮迁移的长度。酪氨酸激酶（TK）抑制剂染料木黄酮和赫司特菌素A也单独抑制上皮迁移。当加入PKC抑制剂或TK抑制剂时，SP和IGF-1对角膜上皮迁移的协同刺激作用消失。TK抑制剂消除了SP和EGF的协同作用，但PKC抑制剂仅部分抑制了该作用。
这些结果表明，SP和EGF的协同作用可能需要TK途径，而SP和IGF-1的协同作用可能需要PKC和TK途径。
