Decorin induced by progesterone plays a crucial role in suppressing endometriosis.
Decorin induced by progesterone plays a crucial role in suppressing endometriosis.
复制标题
DOI：
10.1530/joe-14-0393
复制
发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Ohmichi M
中科院分区：
文献类型：
--
作者：
Ono YJ;Terai Y;Tanabe A;Hayashi A;Hayashi M;Yamashita Y;Kyo S;Ohmichi M
地诺孕素是一种人工合成的孕激素，已被证明对子宫内膜异位症有效，尽管它如何影响异位子宫内膜细胞仍不清楚。核心蛋白聚糖已被证明是一种强大的内源性肿瘤阻遏物，以旁分泌方式发挥作用，以限制肿瘤生长。我们的目的是研究孕酮和地诺孕素对人异位子宫内膜上皮细胞和间质细胞系体外增殖的直接影响，并评估核心蛋白聚糖如何促成这种效果。我们还检测了50例子宫内膜异位症患者DCN mRNA的表达。这两种细胞系的生长均受到核心蛋白聚糖和地诺孕素的剂量依赖性抑制。使用染色质免疫沉淀测定，注意到孕酮和地诺孕素直接诱导EMOsis cc/TERT细胞（永生化的人卵巢上皮细胞）和CRL-4003细胞（永生化的人子宫内膜基质细胞）中核心蛋白聚糖启动子的结合。孕激素和地诺孕素也导致显着诱导细胞周期停滞通过核心蛋白聚糖通过促进生产的p21在两种细胞系中以剂量依赖性的方式。核心蛋白聚糖也抑制MET在两种细胞系中的表达。我们证实了地诺孕素治疗患者的DCN mRNA表达高于对照组。总之，由地诺孕素诱导的核心蛋白聚糖似乎通过产生p21人异位子宫内膜细胞和在位子宫内膜间质细胞而发挥抗增殖作用和诱导细胞周期停滞，在抑制子宫内膜异位症中发挥关键作用。
Dienogest, a synthetic progestin, has been shown to be effective against endometriosis, although it is still unclear as to how it affects the ectopic endometrial cells. Decorin has been shown to be a powerful endogenous tumor repressor acting in a paracrine fashion to limit tumor growth. Our objectives were to examine the direct effects of progesterone and dienogest on the in vitro proliferation of the human ectopic endometrial epithelial and stromal cell lines, and evaluate as to how decorin contributes to this effect. We also examined DCN mRNA expression in 50 endometriosis patients. The growth of both cell lines was inhibited in a dose-dependent manner by both decorin and dienogest. Using a chromatin immunoprecipitation assay, it was noted that progesterone and dienogest directly induced the binding of the decorin promoter in the EMOsis cc/TERT cells (immortalized human ovarian epithelial cells) and CRL-4003 cells (immortalized human endometrial stromal cells). Progesterone and dienogest also led to significant induced cell cycle arrest via decorin by promoting production of p21 in both cell lines in a dose-dependent manner. Decorin also suppressed the expression of MET in both cell lines. We confirmed that DCN mRNA expression in patients treated with dienogest was higher than that in the control group. In conclusion, decorin induced by dienogest appears to play a crucial role in suppressing endometriosis by exerting anti-proliferative effects and inducing cell cycle arrest via the production of p21 human ectopic endometrial cells and eutopic endometrial stromal cells.