TY - JOUR
T1 - Synergistic effect of substance P with epidermal growth factor on epithelial migration in rabbit cornea
AU - Nakamura, Masatsugu
AU - Nishida, Teruo
AU - Ofuji, Keiko
AU - Reid, Ted W.
AU - Mannis, Mark J
AU - Murphy, Christopher J
PY - 1997/9
Y1 - 1997/9
N2 - In order to investigate the role of neural regulation in corneal epithelial healing, we examined the effect of substance P (SP) on corneal epithelial migration using an organ culture system of rabbit corneas. We investigated the synergistic effects of SP with (1) growth factors: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-β (TGF-β); (2) extracellular matrix proteins: fibronectin, vitronectin, laminin, and collagen type IV; and (3) cytokines: interleukin- 1α (IL-1α), IL-1β, and interleukin-6 (IL-6). Rabbit corneal blocks were cultured in the absence or presence of various reagents for 24 hr. The corneal blocks were then fixed, dehydrated, embedded in paraffin and stained by hematoxylin-eosin, and the length of the path of epithelial migration was measured. The addition of SP alone, at concentrations up to 50 μg ml-1, did not affect epithelial migration. EGF, fibronectin, vitronectin, collagen type IV, and IL-6 stimulated epithelial migration, but bFGF, TGF-β, laminin, IL-1α, and IL-1β did not. The stimulatory effect of EGF on the epithelial migration was enhanced by the presence of SP. This synergistic effect of SP and EGF on corneal epithelial migration was abolished by the addition of an SP antagonist or enkephalinase. Other neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acetylcholine chloride, norepinephrine, serotonin) and tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin) were examined, but none exhibited a synergistic effect with EGF. Interestingly, EGF alone stimulated the incorporation of 3H-thymidine into corneal epithelial cells, but the addition of SP with EGF did not enhance this effect. These results demonstrate that SP enhanced the EGF stimulation of corneal epithelial migration in vitro in a specific manner, suggesting a possible role of SP as a modulator of epithelial wound healing.
AB - In order to investigate the role of neural regulation in corneal epithelial healing, we examined the effect of substance P (SP) on corneal epithelial migration using an organ culture system of rabbit corneas. We investigated the synergistic effects of SP with (1) growth factors: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-β (TGF-β); (2) extracellular matrix proteins: fibronectin, vitronectin, laminin, and collagen type IV; and (3) cytokines: interleukin- 1α (IL-1α), IL-1β, and interleukin-6 (IL-6). Rabbit corneal blocks were cultured in the absence or presence of various reagents for 24 hr. The corneal blocks were then fixed, dehydrated, embedded in paraffin and stained by hematoxylin-eosin, and the length of the path of epithelial migration was measured. The addition of SP alone, at concentrations up to 50 μg ml-1, did not affect epithelial migration. EGF, fibronectin, vitronectin, collagen type IV, and IL-6 stimulated epithelial migration, but bFGF, TGF-β, laminin, IL-1α, and IL-1β did not. The stimulatory effect of EGF on the epithelial migration was enhanced by the presence of SP. This synergistic effect of SP and EGF on corneal epithelial migration was abolished by the addition of an SP antagonist or enkephalinase. Other neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acetylcholine chloride, norepinephrine, serotonin) and tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin) were examined, but none exhibited a synergistic effect with EGF. Interestingly, EGF alone stimulated the incorporation of 3H-thymidine into corneal epithelial cells, but the addition of SP with EGF did not enhance this effect. These results demonstrate that SP enhanced the EGF stimulation of corneal epithelial migration in vitro in a specific manner, suggesting a possible role of SP as a modulator of epithelial wound healing.
KW - Cornea
KW - Epidermal growth factor
KW - Epithelial migration
KW - Extracellular matrix proteins
KW - Growth factors
KW - Interleukins
KW - Substance P
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U2 - 10.1006/exer.1997.0345
DO - 10.1006/exer.1997.0345
M3 - Article
C2 - 9299169
AN - SCOPUS:0030866765
VL - 65
SP - 321
EP - 329
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
IS - 3
ER -