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


METHODS
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.


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 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.


CONCLUSIONS
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.
Ofuji
K
K
Department of Ophthalmology, Yamaguchi University School of Medicine, Ube City, Japan.
Nakamura
M
M
Nishida
T
T
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019573:Epithelium, Corneal / Q000166:cytology* / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009924:Organ Culture Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013373:Substance P; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C