Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14
Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14
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DOI：
10.1124/jpet.104.076075
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发表时间：
2005-03-01
影响因子：
3.5
通讯作者：
Schuster, G
中科院分区：
文献类型：
--
作者：
Hsu, S;Yamamoto, T;Schuster, G
表没食子儿茶素没食子酸酯（Epigallocatechin-3-gallate，EGCG）是绿色茶中含量最丰富的多酚类物质，通过选择性诱导肿瘤细胞凋亡发挥化学预防作用。相反，EGCG加速正常人表皮角质形成细胞（NHEK）的终末分化，部分通过上调p57/KIP 2介导，p57/KIP 2是一种细胞周期蛋白依赖性激酶抑制剂，可导致生长停滞和分化。然而，目前还不清楚，如果表没食子儿茶素没食子酸酯调节半胱天冬酶14，一个独特的调节上皮细胞终末分化与角化。在这里，我们研究了EGCG对NHEK中caspase 14表达的影响，并将p57/KIP 2的蛋白和mRNA表达与正常角质形成细胞或p57/KIP 2表达的肿瘤细胞（OSC 2，口腔鳞状细胞癌细胞系）中caspase 14的蛋白和mRNA表达相关联。此外，石蜡包埋的正常和未经治疗的银屑病（异常角化）皮肤切片从人类进行了评估半胱天冬酶14的免疫组织化学。在NHEK中，EGCG在24小时内诱导caspase 14 mRNA和蛋白水平的表达。p57/KIP 2在OSC 2细胞中的表达足以在没有EGCG的情况下诱导caspase 14;这种caspase 14的诱导被转化生长因子β 1下调。在人类银屑病皮肤样本中，上表皮中的半胱天冬酶14染色减少，尤其是在核区域。这些结果表明，除了p57/KIP 2，EGCG诱导的表皮角质形成细胞的终末分化涉及caspase 14的上调。进一步了解EGCG如何调节细胞分化可能有助于开发用于选定临床应用的绿色茶制剂。
Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-beta1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.