Qin Haiyan, Zhang Guang, Zhang Lianbo
Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Exp Ther Med. 2018 Apr;15(4):3439-3448. doi: 10.3892/etm.2018.5863. Epub 2018 Feb 13.
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 β-galactosidase (SA-β-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.
多梳蛋白家族基因（PcG）编码参与细胞分化、增殖和衰老过程表观遗传调控的染色质修饰蛋白。PcG复合物的关键亚基，即zeste 2多梳抑制复合物2亚基增强子（EZH2），在多种机制中发挥核心作用，如染色质结构形成、基因表达调控和DNA损伤。在本研究中，使用紫外线A（UVA）照射人皮肤成纤维细胞以构建光老化细胞模型。随后，进行了细胞活力测定、Hoechst染色、流式细胞术检测细胞凋亡、衰老相关β-半乳糖苷酶（SA-β-gal）染色和红细胞排斥实验。EZH2的组蛋白甲基化酶抑制剂GSK126用作实验因素。结果表明，GSK126下调EZH2的mRNA表达水平并上调BMI-1的mRNA表达水平。值得注意的是，GSK126影响各种光老化相关基因的转录，从而抵御UVA辐射诱导的光老化。
