启动子区DNA去甲基化增强子宫内膜异位症患者子宫内膜基质细胞MMP-9的表达

DNA demethylation at the promoter region enhances the expression of MMP-9 in ectopic endometrial stromal cells of endometriosis

目的研究子宫内膜异位症中基质金属蛋白酶9(MMP-9)基因表达的DNA甲基化调控机制。方法采用甲基化特异性PCR检测在位与异位子宫内膜组织中MMP-9 mRNA的表达,采用免疫组织化学染色检测在位与异位子宫内膜组织中MMP-9蛋白的表达。原代培养子宫内膜异位基质细胞,细胞经5-杂氮-2'-脱氧胞苷(5-Aza-dC)处理后,分析MMP-9基因的表达及其启动子甲基化状态。结果异位子宫内膜组织中MMP-9 mRNA和蛋白的表达高于在位子宫内膜组织。异位子宫内膜组织中MMP-9基因启动子区DNA甲基化水平低于在位子宫内膜组织。5-Aza-dC处理异位子宫内膜细胞后,MMP-9的表达水平升高,MMP-9基因启动子区出现明显的去甲基化。结论 MMP-9基因启动子区DNA去甲基化增强子宫内膜异位症患者异位内膜基质细胞中MMP-9的表达。

Objective To investigate the role of DNA methylation in the regulation of matrix metalloproteinase9（MMP-9）gene expression in endometriosis. Methods MMP-9 gene methylation status in eutopic and ectopic endometria were analyzed by methylation specific PCR. The expression of MMP-9 protein in eutopic and ectopic endometria were detected by immunohistochemistry. We prepared the primary cultured ectopic endometrial stromal cells,and then examined the gene expression and methylation status of MMP-9 after the culture cells were treated with 5-Aza-2-deoxycytidine. Results The expression of MMP-9 in ectopic endometrial stromal cells was significantly higher than that in eutopic endometrium. MMP-9methylation level was lower in ectopic endometrium. After treated with 5-Aza-dC,endometriosis cells showed elevated MMP-9 gene expression and methylation level. Conclusion DNA methylation at the promoter region of MMP-9 gene can enhance the expression of MMP-9 in ectopic endometrial stromal cells of endometriosis.