系统性硬化症患者外周血 B 细胞中的组蛋白修饰异常。
Aberrant histone modification in peripheral blood B cells from patients with systemic sclerosis.
机构信息
Department of Dermatology, Second Xiangya Hospital, Central South University, 139 Ren-Min Road, Changsha 410011, China.
出版信息
Clin Immunol. 2013 Oct;149(1):46-54. doi: 10.1016/j.clim.2013.06.006. Epub 2013 Jun 20.
OBJECTIVES
To investigate alterations in histone modifications in B cells and their role in the pathogenesis of systemic sclerosis (SSc).
METHODS
Global histone H3/H4 acetylation and H3K4/H3K9 methylation in B cells of SSc were tested by EpiQuik™ assay kits. Related histone modifier enzymes were measured by RT-PCR and Western blot.
RESULTS
Global histone H4 hyperacetylation and global histone H3K9 hypomethylation were observed in SSc B cells compared with controls. Expression of JHDM2A was significantly increased but HDAC2, HDAC7, and, SUV39H2 were significantly down-regulated in SSc B cells relative to controls. Global histone H4 acetylation and the expression of HDAC2 were negatively correlated. Global histone H3K9 methylation and the expression of SUV39H2 protein were positively correlated. Global H4 acetylation was positively correlated with disease activity and expression of HDAC2 protein was negatively correlated with skin thickness.
CONCLUSIONS
Histone modifications were altered in B cells in SSc correlating with skin thickness and disease activity.
目的
研究系统性硬化症（SSc）患者 B 细胞中组蛋白修饰的改变及其在发病机制中的作用。
方法
通过 EpiQuik™检测试剂盒检测 SSc B 细胞中的组蛋白 H3/H4 乙酰化和 H3K4/H3K9 甲基化。通过 RT-PCR 和 Western blot 测定相关组蛋白修饰酶。
结果
与对照组相比，SSc B 细胞中观察到组蛋白 H4 过度乙酰化和组蛋白 H3K9 低甲基化。与对照组相比，SSc B 细胞中 JHDM2A 的表达显著增加，而 HDAC2、HDAC7 和 SUV39H2 的表达则显著下调。组蛋白 H4 乙酰化与 HDAC2 的表达呈负相关。组蛋白 H3K9 甲基化与 SUV39H2 蛋白的表达呈正相关。组蛋白 H4 乙酰化与疾病活动度呈正相关，而 HDAC2 蛋白的表达与皮肤厚度呈负相关。
结论
SSc 患者 B 细胞中的组蛋白修饰发生改变，与皮肤厚度和疾病活动度相关。
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