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甘草酸减弱人真皮乳头细胞的干细胞样表型。

Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells.

作者信息

Kiratipaiboon Chayanin, Tengamnuay Parkpoom, Chanvorachote Pithi

机构信息

Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

Phytomedicine. 2015 Dec 15;22(14):1269-78. doi: 10.1016/j.phymed.2015.11.002. Epub 2015 Nov 14.

Abstract

BACKGROUND

Although the growth of unwanted hair or hirsutism is a harmless condition, many people find it bothersome and embarrassing. Maintaining stem cell features of dermal papilla cells is a critical biological process that keeps the high rate of hair growth. Glycyrrhizic acid has been reported to impair hair growth in some studies; however, its underlying mechanism has not yet been investigated.

PURPOSE

This study aimed to explore the effect and underlying mechanism of glycyrrhizic acid on stemness of human dermal papilla cells.

STUDY DESIGN/METHODS: The stem cell molecular markers, epithelial to mesenchymal markers and Wnt/β-catenin-associated proteins of human dermal papilla cell line and primary human dermal papilla cells were analysed by western blot analysis and immunocytochemistry.

RESULTS

The present study demonstrated that glycyrrhizic acid significantly depressed the stemness of dermal papilla cells in dose- and time-dependent manners. Clonogenicity and stem cell markers in the glycyrrhizic acid-treated cells were found to gradually decrease in the culture in a time-dependent manner. Our results demonstrated that glycyrrhizic acid exerted the stem cell suppressing effects through the interruption of ATP-dependent tyrosine kinase/glycogen synthase kinase3β-dependent mechanism which in turn down-regulated the β-catenin signalling pathway, coupled with decreased its down-stream epithelial-mesenchymal transition and self-renewal transcription factors, namely, Oct-4, Nanog, Sox2, ZEB1 and Snail. The effect of glycyrrhizic acid on the reduction of stem cell features was also observed in the primary dermal papilla cells directly obtained from human hair follicles.

CONCLUSION

These results revealed a novel molecular mechanism of glycyrrhizic acid in regulation of dermal papilla cells and provided the evidence supporting the use of this compound in suppressing the growth of unwanted hair.

摘要

背景

尽管毛发过多或多毛症的生长是一种无害状况,但许多人觉得它令人烦恼且尴尬。维持毛乳头细胞的干细胞特性是保持高毛发增长率的关键生物学过程。在一些研究中,甘草酸已被报道会损害毛发生长;然而,其潜在机制尚未得到研究。

目的

本研究旨在探讨甘草酸对人毛乳头细胞干性的影响及其潜在机制。

研究设计/方法:通过蛋白质免疫印迹分析和免疫细胞化学分析人毛乳头细胞系和原代人毛乳头细胞的干细胞分子标志物、上皮-间质标志物以及Wnt/β-连环蛋白相关蛋白。

结果

本研究表明,甘草酸以剂量和时间依赖性方式显著降低毛乳头细胞的干性。在培养过程中,发现甘草酸处理的细胞中的克隆形成能力和干细胞标志物以时间依赖性方式逐渐降低。我们的结果表明,甘草酸通过中断ATP依赖性酪氨酸激酶/糖原合酶激酶3β依赖性机制发挥干细胞抑制作用,这反过来下调β-连环蛋白信号通路,同时降低其下游的上皮-间质转化和自我更新转录因子,即Oct-4、Nanog、Sox2、ZEB1和Snail。在直接从人毛囊获得的原代毛乳头细胞中也观察到了甘草酸对干细胞特性降低的影响。

结论

这些结果揭示了甘草酸调节毛乳头细胞的一种新分子机制,并为支持使用该化合物抑制多余毛发的生长提供了证据。

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