Participation of p38 MAP kinase, but not p44/42 MAP kinase, in stimulation of corneal epithelial migration by substance P and IGF-1.
OBJECTIVE
Substance P and insulin-like growth factor-1 (IGF-1) synergistically promote corneal epithelial migration both in vitro and in vivo. The mechanism of this action was investigated.


METHODS
The effects of various inhibitors and activators of intracellular signaling pathways on corneal epithelial migration were examined by measuring the length of the migration path in rabbit corneal blocks in culture.


RESULTS
Inhibitors of signaling by p38 or p44/42 isoforms of mitogen-activated protein (MAP) kinase or of phosphatidylinositol (PI) 3-kinase reduced the extent of spontaneous migration of the corneal epithelium, whereas modulators of signaling by cyclic AMP- or cyclic GMP-dependent protein kinases had no effect. The inhibitors of p38 MAP kinase and of PI 3-kinase also abolished the stimulatory effect of substance P and IGF-1 on epithelial migration, whereas inhibitors of signaling by p44/42 MAP kinase or modulators of cyclic nucleotide-dependent signaling did not.


CONCLUSIONS
These results suggest that various signal transduction systems participate in spontaneous corneal epithelial migration as well as in the combined effect of substance P and IGF-1 on this process. In particular, although both p38 and p44/42 isoforms of MAP kinase appear to regulate spontaneous corneal epithelial migration, the stimulatory effect of substance P and IGF-1 appears to be mediated by p38 MAP kinase but not by p44/42 MAP kinase.
Nakamura
Masatsugu
M
Department of Biomolecular Recognition and Ophthalmology, Yamaguchi University School of Medicine, Yamaguchi, Japan. nakamuram@santen.co.jp
Chikama
Tai-Ichiro
T
Nishida
Teruo
T
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D004357:Drug Synergism; D019573:Epithelium, Corneal / Q000166:cytology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D013373:Substance P; D007334:Insulin-Like Growth Factor I; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases