Synergistic effects of substance P with insulin-like growth factor-1 on epithelial migration of the cornea.
We find that substance P (SP) and insulin-like growth factor-1 (IGF-1) demonstrate a synergistic effect on the stimulation of rabbit corneal epithelial migration in an organ culture. The addition of either SP or IGF-1 alone did not affect epithelial migration, while the combination of SP and IGF-1 stimulated epithelial migration in a dose-dependent fashion. The synergistic effects of SP and IGF-1 on corneal epithelial migration were nulled by the addition of a SP antagonist or enkephalinase. Among neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acethylcholine chloride, norepinephrine, serotonin) or tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin), only SP demonstrated a synergistic effect with IGF-1 on cellular migration. In contrast, the combination of SP and IGF-1 did not affect the incorporation of 3H-thymidine into corneal epithelial cells. The attachment of the corneal epithelial cells to fibronectin, collagen type IV, and laminin matrices increased after treatment of the cells with SP and IGF-1, but SP or IGF-1 by themselves did not affect the attachment of the cells to these extracellular matrix proteins. An identical synergistic effect on corneal epithelial migration was observed when an NK-1 receptor agonist was used in place of SP, suggesting the synergistic effect of SP and IGF-1 might be mediated through the NK-1 receptor system. These results suggest that the maintenance of the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors.
Nishida
T
T
Department of Ophthalmology, Yamaguchi University School of Medicine, Japan.
Nakamura
M
M
Ofuji
K
K
Reid
T W
TW
Mannis
M J
MJ
Murphy
C J
CJ
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003315:Cornea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004357:Drug Synergism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015260:Neprilysin / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D011817:Rabbits; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D009479:Neuropeptides; D018040:Receptors, Neurokinin-1; D013373:Substance P; D007334:Insulin-Like Growth Factor I; D015260:Neprilysin; D013936:Thymidine