Kanzaki Yukari, Onoue Fumikazu, Ishikawa Fuyuki, Ide Toshinori
Department of Cellular and Molecular Biology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Hiroshima City, Hiroshima 734-8551, Japan.
Exp Cell Res. 2002 Oct 1;279(2):321-9. doi: 10.1006/excr.2002.5607.
Changes in expression levels of various cytokines, growth factors, and related genes were examined by reverse transcriptase polymerase chain reaction in a normal human fibroblast cell strain, TIG-3, along with in vitro aging. The expression levels of KGF and IGF-II were decreased with proliferative aging but not by growth arrest of young cells. In telomere-elongated cells prepared by transfection with human telomerase reverse transcriptase cDNA, high expression levels of these two genes were maintained, suggesting a causal relation between telomere shortening and reduced expression of KGF and IGF-II. The expression level of HGF was high in both growing and growth-arrested young cells but low in both senescent and telomere-elongated cells. The expression levels of follistatin and HB-EGF were high in both young growing and telomere-elongated cells but low in both senescent and growth-arrested young cells, indicating a growth-dependent expression. Expression levels of FGF-1, FGF-2, VEGF, BMP-3, and amphiregulin did not change with proliferative aging, growth arrest of young cells, or telomere elongation and life-span extension.
在正常人成纤维细胞系TIG-3中,随着体外衰老,通过逆转录聚合酶链反应检测了各种细胞因子、生长因子及相关基因表达水平的变化。角质形成细胞生长因子(KGF)和胰岛素样生长因子-II(IGF-II)的表达水平随增殖性衰老而降低,但不因年轻细胞的生长停滞而降低。在用人类端粒酶逆转录酶cDNA转染制备的端粒延长细胞中,这两个基因维持高表达水平,提示端粒缩短与KGF和IGF-II表达降低之间存在因果关系。肝细胞生长因子(HGF)在生长和生长停滞的年轻细胞中表达水平均较高,但在衰老细胞和端粒延长细胞中均较低。卵泡抑素和肝素结合表皮生长因子(HB-EGF)在年轻生长细胞和端粒延长细胞中表达水平均较高,但在衰老细胞和生长停滞的年轻细胞中均较低,表明其表达依赖于生长。成纤维细胞生长因子-1(FGF-1)、成纤维细胞生长因子-2(FGF-2)、血管内皮生长因子(VEGF)、骨形态发生蛋白-3(BMP-3)和双调蛋白的表达水平不会随增殖性衰老、年轻细胞的生长停滞、端粒延长及寿命延长而发生改变。