GSK126 (EZH2 inhibitor) interferes with ultraviolet A radiation-induced photoaging of human skin fibroblast cells
GSK126 (EZH2 inhibitor) interferes with ultraviolet A radiation-induced photoaging of human skin fibroblast cells
复制标题
GSK126（EZH2抑制剂）干扰紫外线A辐射诱导的人皮肤成纤维细胞光老化
DOI：
10.3892/etm.2018.5863
复制
发表时间：
2018-04-01
影响因子：
2.7
通讯作者：
Zhang, Lianbo
中科院分区：
文献类型：
--
作者：
Qin, Haiyan;Zhang, Guang;Zhang, Lianbo
多梳组基因（Polycomb group genes，PcG）编码的染色质修饰蛋白参与细胞分化、增殖和衰老过程的表观遗传调控。PcG复合物的关键亚基，增强子zeste 2多梳抑制复合物2亚基（EZH 2），在多种机制中具有中心作用，如染色质结构的形成，基因表达调控和DNA损伤。本研究采用长波紫外线（UVA）照射人皮肤成纤维细胞，建立光老化细胞模型。随后进行细胞活力测定、Hoechst染色、流式细胞术检测凋亡、衰老相关半乳糖苷酶（SA-gal）染色和红细胞排斥实验。以EZH 2的组蛋白甲基化酶抑制剂GSK 126为实验因子。结果表明，GSK 126下调EZH 2 mRNA表达水平，上调BMI-1 mRNA表达水平。值得注意的是，GSK 126影响各种光老化相关基因的转录，从而保护免受UVA辐射诱导的光老化。
Polycomb group genes (PcG) encode chromatin modification proteins that are involved in the epigenetic regulation of cell differentiation, proliferation and the aging processes. The key subunit of the PcG complex, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), has a central role in a variety of mechanisms, such as the formation of chromatin structure, gene expression regulation and DNA damage. In the present study, ultraviolet A (UVA) was used to radiate human dermal fibroblasts in order to construct a photo-aged cell model. Subsequently, the cell viability assay, Hoechst staining, apoptosis detection using flow cytometry, senescence-associated -galactosidase (SA--gal) staining and erythrocyte exclusion experiments were performed. GSK126, a histone methylation enzyme inhibitor of EZH2, was used as an experimental factor. Results suggested that GSK126 downregulated the mRNA expression levels of EZH2 and upregulated the mRNA expression levels of BMI-1. Notably, GSK126 affected the transcription of various photoaging-related genes and thus protected against photoaging induced by UVA radiation.