Up-regulation of integrin alpha5 by a C-terminus four-amino-acid sequence of substance P (phenylalanine-glycine-leucine-methionine- amide) synergistically with insulin-like growth factor-1 in SV-40 transformed human corneal epithelial cells.
We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial migration in vivo and in vitro. We investigated whether the substance P-derived tetrapeptide (phenylalanine-glycine-leucine-methionine-amide, FGLM) can up-regulate the receptors for fibronectin and cellular adhesion to fibronectin matrix in the presence or absence of IGF-1 in cultured SV-40 transformed human corneal epithelial (HCE) cells. The combination of both FGLM and IGF-1 and substance P and IGF-1 significantly increased the number of cells adhered to the fibronectin matrix and the expression of integrin alpha5. The synergistic effect of FGLM and IGF-1 on the adhesion of HCE cells to the fibronectin matrix is partly carried through up-regulation of integrin alpha5 expression in HCE cells. These results showed that the four-amino-acid sequence at the C-terminus of substance P completely mimics the substance P molecule in terms of synergism with IGF-1 on adhesion of epithelial cells to the fibronectin matrix.
Department of Ophthalmology, Yamaguchi University School of Medicine, 1144 Kogushi, Yamaguchi, Ube City, 755-8505, Japan. chikama@po.cc.yamaguchi-u.ac.jp
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Nakamura
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Nishida
D015703:Antigens, CD / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003315:Cornea / Q000821:virology*; D004357:Drug Synergism; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D039564:Integrin alphaV; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D013373:Substance P / Q000737:chemistry*; D014170:Transformation, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*
D015703:Antigens, CD; D005353:Fibronectins; D039564:Integrin alphaV; D009842:Oligopeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; C112946:phenylalanyl-glycyl-leucyl-methioninamide; D013373:Substance P; D007334:Insulin-Like Growth Factor I