Studies on the age-related decline in the migration of human skin fibroblasts into a denuded area in a cell monolayr

关于人类皮肤成纤维细胞迁移到单层细胞裸露区域的年龄相关性下降的研究

• 批准号: 05834018
• 负责人: KONDO Hiroshi
• 金额: $ 1.47万
• 依托单位: Tokyo Metropolitan Institute of Gerontology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05834018/
• 关键词: human skin fibroblast; cell migration; age-related decline; growth factor; bFGF; PDGF; collagen; 細胞老化; マトリックス物質; 遊走調節因子

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.

人类皮肤成纤维细胞的迁移随体外和体内（供体年龄）衰老而下降。为了了解与年龄相关的下降的机制，我们试图确定调节细胞迁移的因素，并证明人类胎儿皮肤成纤维细胞的迁移是由BFGF刺激的，BFGF是由自身产生的，胶原蛋白（胎儿表型）的迁移，而成人毛皮细胞受pdgf和collage的刺激（成人）的迁移，而collake则是成人毛皮的迁移。 PDGF刺激了新生儿成纤维细胞迁移，以找到两种表型的差异，胎儿成纤维细胞的迁移是在出生前发生的。 Northern印迹分析表明，在检查所有人类皮肤成纤维细胞中检测到FGFR-1 mRNA，而未检测到其他三个FGFR mRNA（2,3,4）。 FGFR-1 mRNA在人体皮肤成纤维细胞中的表达似乎是偶然降低的供体年龄，这表明FGFR.NEXT并未解释胎儿形式的表型过渡，研究了细胞迁移与胶原蛋白合成之间的关系。互间杀伤了人类胎儿皮肤纤维纤维细胞的迁移。这种抑制是特异性的，因为中和抗互化 - 抗抗体逆转了干扰素-beta诱导的细胞迁移的抑制。在100 IU/ML干扰素β下抑制了collagen的合成，在抑制成纤维细胞迁移的浓度下，抑制了抑制。另一方面，人类成年血清抑制了人胎儿皮肤成纤维细胞迁移以及胶原蛋白的合成。这些结果表明，细胞迁移的抑制与胶原蛋白合成的降低之间存在很强的相关性，这表明皮肤成纤维细胞迁移与年龄相关的下降很大程度上是由于胶原蛋白。

项目成果

近藤 昊、武内恒成、米沢由美子、伊藤信行、渡辺和忠: "ヒト皮膚線維芽細胞の遊走の加齢変化と遊走調節因子:bFGFとFGFレセプター" 基礎老化研究. 18. 336-337 (1994)

Akira Kondo、Tsunenari Takeuchi、Yumiko Yonezawa、Nobuyuki Ito、Kazutada Watanabe：“人类皮肤成纤维细胞迁移的老化变化和迁移调节器：bFGF 和 FGF 受体”基础老化研究 18. 336-337 (1994)。

Hiroshi Kondo,Mark A.Lane,et al.: "Effects of aging and dietary restriction on activity of monkey serum in promoting fibroblast migration" Mech.Ageing Dev.(in press). (1995)

Hiroshi Kondo、Mark A.Lane 等人：“衰老和饮食限制对猴血清促进成纤维细胞迁移活性的影响”Mech.Ageing Dev.（出版中）。

Hiroshi kondo & Yumiko Yonezawa: "Age-related changes in the migration of human fibroblasts and migration-regulating factors" The XVth Congress of the International Association of Gerontology. 93 (1993)

近藤浩

Hiroshi Kondo, et al.: "Effects of aging and dietary restriction on activity of monkey serun in promoting fibroblast migration" Mech. Ageing Dev.(in press). (1995)

Hiroshi Kondo 等人：“衰老和饮食限制对猴血清促进成纤维细胞迁移活性的影响”Mech。

Hiroshi kondo & Yumiko Yonezawa: "Regulation of the migration of human skin fibroblasts by growth factor: Fetal-adult transition" Zool.Sci.Suppl.93. 158 (1993)

近藤浩