Signaling regulation for synergistic effects of substance P and insulin-like growth factor-1 or epidermal growth factor on corneal epithelial migration

Purpose: In a previous report we showed that substance P (SP) and insulin-l ike growth factor-1 (IGF-1) or epidermal growth factor (EGF) synergisticall y stimulate corneal epithelial migration. In this study, we used an organ c ulture system of rabbit cornea to identify which signal transduction system affects corneal epithelial migration. Methods: Rabbit corneal blocks were cultured in TC-199 culture medium conta ining various reagents for 24 hours. After the end of cultivation, the leng th of the path of epithelial migration was measured. Results: 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 o n corneal epithelial migration were eliminated when PKC inhibitors or TK in hibitors were added. The synergistic effect of SP and EGF was eliminated by TK inhibitors, but only partly suppressed by PKC inhibitors. Conclusions: These results suggest that the synergistic effect of SP and EG F might require a TK pathway, and that the synergistic effect of SP and TGF -1 might require both PKC and TK pathways. (C) 2000 Japanese Ophthalmologic al Society.