| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
The migration of human skin fibroblasts declined with in vitro and in vivo(donor age) aging. To understand the mechanism of the age-related decline, we tried to determine the factors which regulate cell migration and demonstrated that the migration of human fetal skin fibroblasts was stimulated by bFGF,which was produced by themselves, and collagen (fetal phenotype), whereas the migration of adult-donor skin fibroblasts was stimulated by PDGF and collagen (adult phenotype). The fetal-adult phenotype transition occurred before birth because newborn fibroblast migration was stimulated by PDGF.To find the difference of the two phenotypes, whether FGF receptor (FGFR) mRNA expression in fetal skin fibroblasts differs from those in adult and old skin fibroblasts was studied. Northern blot analysis demonstrated that FGFR-1 mRNA was detected in all human skin fibroblasts examined and the other three FGFR mRNA (type2,3,4) were not detected. The expression of FGFR-1 mRNA in human skin fibroblasts seemed to decrease inversely to donor age, suggesting that fetal-adult phenotype transition is not explained by FGFR.Next, the relationship between cell migration and collagen synthesis was investigated.Interferon-betasuppressed the migration of human fetal skin fibroblasts. The inhibition was specific because neutralizing anti-interferon-betaantibody reversed the inhibition of cell migration induced by interferon-beta.Collagen synthesis was inhibited at 100 IU/ml interferon-beta, at the concentration of which fibroblast migration was suppressed. On the other hand, human adult serum suppressed human fetal skin fibroblast migration as well as collagen synthesis. These results indicate the strong correlation between the inhibition of cell migration and the decrease of collagen synthesis, suggesting that age-related decline in skin fibroblast migration is largely due to collagen.
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