Article date: May 1999
By: Masatsugu Nakamura, Tai‐ichiro Chikama, Teruo Nishida, in Volume 127, Issue 2, pages 489-497
We previously reported that substance P and insulin‐like growth factor‐1 (IGF‐1) synergistically stimulate corneal epithelial wound healing in vitro and in vivo. We wished to identify which portion of the amino acid sequence of substance P might be responsible for this synergism.
Corneal epithelial migration was not affected by the addition of any one of the following factors: substance P; Phe‐Gly‐Leu‐Met‐NH2 (C‐terminal of substance P); Val‐Gly‐Leu‐Met‐NH2 (C‐terminal of neurokinin A, neurokinin B, and kassinin); Tyr‐Gly‐Leu‐Met‐NH2 (C‐terminal of physalaemin); Ile‐Gly‐Leu‐Met‐NH2 (C‐terminal of eledoisin); or Gly‐Leu‐Met‐NH2 (common C‐terminal of tachykinins).
In the presence of IGF‐1, only substance P and Phe‐Gly‐Leu‐Met‐NH2 were synergistic in stimulating corneal epithelial migration in a dose‐dependent fashion.
The combination of Phe‐Gly‐Leu‐Met‐NH2 and IGF‐1 did not affect the incorporation of [3H]‐thymidine into corneal epithelial cells.
Treatment with Phe‐Gly‐Leu‐Met‐NH2 and IGF‐1, but not with Phe‐Gly‐Leu‐Met‐NH2 or IGF‐1 alone, increased attachment of corneal epithelial cells to a fibronectin matrix.
The levels of α5 and β1 integrin were not affected by Phe‐Gly‐Leu‐Met‐NH2 or IGF‐1 alone, but they were significantly increased by the combination of Phe‐Gly‐Leu‐Met‐NH2 and IGF‐1.
Topical application of the same combination facilitated corneal epithelial wound closure in vivo.
These results demonstrated that Phe‐Gly‐Leu‐Met‐NH2, a sequence of 4 amino‐acids of the C‐terminal of substance P, is the minimum sequence necessary to produce the synergistic effects of substance P and IGF‐1 on corneal epithelial wound healing.
We previously reported that substance P and insulin‐like growth factor‐1 (IGF‐1) synergistically stimulate corneal epithelial wound healing in vitro and in vivo. We wished to identify which portion of the amino acid sequence of substance P might be responsible for this synergism.
Corneal epithelial migration was not affected by the addition of any one of the following factors: substance P; Phe‐Gly‐Leu‐Met‐NH2 (C‐terminal of substance P); Val‐Gly‐Leu‐Met‐NH2 (C‐terminal of neurokinin A, neurokinin B, and kassinin); Tyr‐Gly‐Leu‐Met‐NH2 (C‐terminal of physalaemin); Ile‐Gly‐Leu‐Met‐NH2 (C‐terminal of eledoisin); or Gly‐Leu‐Met‐NH2 (common C‐terminal of tachykinins).
In the presence of IGF‐1, only substance P and Phe‐Gly‐Leu‐Met‐NH2 were synergistic in stimulating corneal epithelial migration in a dose‐dependent fashion.
The combination of Phe‐Gly‐Leu‐Met‐NH2 and IGF‐1 did not affect the incorporation of [3H]‐thymidine into corneal epithelial cells.
Treatment with Phe‐Gly‐Leu‐Met‐NH2 and IGF‐1, but not with Phe‐Gly‐Leu‐Met‐NH2 or IGF‐1 alone, increased attachment of corneal epithelial cells to a fibronectin matrix.
The levels of α5 and β1 integrin were not affected by Phe‐Gly‐Leu‐Met‐NH2 or IGF‐1 alone, but they were significantly increased by the combination of Phe‐Gly‐Leu‐Met‐NH2 and IGF‐1.
Topical application of the same combination facilitated corneal epithelial wound closure in vivo.
These results demonstrated that Phe‐Gly‐Leu‐Met‐NH2, a sequence of 4 amino‐acids of the C‐terminal of substance P, is the minimum sequence necessary to produce the synergistic effects of substance P and IGF‐1 on corneal epithelial wound healing.
British Journal of Pharmacology (1999) 127, 489–497; doi:10.1038/sj.bjp.0702550
DOI: 10.1038/sj.bjp.0702550
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