Sensitizing effect of substance P on corneal epithelial migration induced by IGF-1, fibronectin, or interleukin-6.
OBJECTIVE
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.
Yamada
Naoyuki
N
Department of Biomolecular Recognition, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Yanai
Ryoji
R
Inui
Makoto
M
Nishida
Teruo
T
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019573:Epithelium, Corneal / Q000166:cytology*; D005353:Fibronectins / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D011817:Rabbits; D013373:Substance P / Q000502:physiology*
D005353:Fibronectins; D015850:Interleukin-6; D009842:Oligopeptides; C112946:phenylalanyl-glycyl-leucyl-methioninamide; D013373:Substance P; D007334:Insulin-Like Growth Factor I