Reversible Regulation of Cell Cycle-Related Genes by Epigallocatechin Gallate for Hibernation of Neonatal Human Tarsal Fibroblasts

Reversible Regulation of Cell Cycle-Related Genes by Epigallocatechin Gallate for Hibernation of Neonatal Human Tarsal Fibroblasts
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DOI:
10.3727/096368909788809776
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发表时间:
2009-01-01
影响因子:
3.3
通讯作者:
Hyon, Suong-Hyu
Hyon, Suong-Hyu
中科院分区:
医学4区
文献类型:
--
作者:
Bae, Jung Yoon;Kanamune, Jun;Hyon, Suong-Hyu

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我们通过分析细胞周期相关基因的表达,研究了表没食子儿茶素没食子酸酯(EGCG)对新生人睑板成纤维细胞(nHTFs)的冬眠作用。将EGCG施加到培养基中适度抑制nHTFs的生长,并且从培养基中去除EGCG导致细胞生长完全恢复。EGCG使S期和G(2)/M期细胞数略有减少,而G(0)/G(1)期细胞数增加。Bill在去除EGCG后,该细胞周期谱恢复到初始水平。细胞周期蛋白D1(CCND 1)的表达。CCNE 2、CCN依赖性激酶6(CDK 6)和CDK 2恢复,而CCNA、CCNB 1和CDK 1不可逆地减弱。通过cDNA微阵列分析的大量基因的表达受到EGCG应用的影响,并且这些受影响的表达水平在去除EGCG后恢复到正常水平。我们还发现FITC-EGCG掺入到nHTFs的胞质溶胶中并进一步核转位,这可能导致针对细胞应答(包括增殖和细胞周期进展)的基因的外源信号的调节。这些结果表明,EGCG不仅暂时影响与细胞周期相关的基因,还影响各种其他细胞功能。
We investigated the hibernation effect of epigallocatechin-3-O-gallate (EGCG) on neonatal human tarsal fibroblasts (nHTFs) by analyzing the expression of cell cycle-related genes. EGCG application to Culture media moderately inhibited the growth of nHTFs, and the removal of EGCG from Culture media led to complete recovery of cell growth. EGCG resulted in a slight decrease in the cell Population of the S and G(2)/M phases of cell cycle with concomitant increase in that of the G(0)/G(1) phase. bill this cell cycle profile was restored to the initial level after EGCG removal. The expression of cyclin D1 (CCND1). CCNE2, CCN-dependent kinase 6 (CDK6), and CDK2 was restored, whereas that of CCNA, CCNB1, and CDK1 was irreversibly attenuated. The expression of a substantial number of genes analyzed by cDNA microarray was affected by EGCG application, and these affected expression levels were restored to the normal levels after EGCG removal. We also found the incorporation of FITC-EGCG into the cytosol of nHTFs and its further nuclear translocation, which might lead to the regulation of the exogenous signals directed to genes for cellular responses including proliferation and cell cycle progression. These results suggest that EGCG temporarily affects not only genes related to the cell cycle but also various other cellular functions.