Department of Gynaecology and Obstetrics of Hainan People's Hospital, Hai Kou 570311, China.
Asian Pac J Trop Med. 2013 Oct;6(10):826-30. doi: 10.1016/S1995-7645(13)60146-7.
To study the effect of estrogen on anovulatory dysfunctional uterine bleeding (ADUB).
Primary endometrial epithelial cells of Hainan Lizu female was cultured and hydrolytic activity of gelatinase was determined by gelatin zymography analysis. Cellular mRNA and protein synthesis was blocked respectively to determine whether the increased expression of MMP-2/9 was induced by estrogen. The expression of VEGF was blocked by siRNA. After treatment with various factors, MMP-9, VEGF, total Erk and phosphorylated Erk expression in primary uterine epithelial cells was detected by Western blotting analysis. Cell MMP-2/9mRNA levels was measured by real-time RT-PCR.
The activity and expression of MMP2/9 was increased in the endometrium of patients with ADUB. Estrogen could up-regulate the expression of VEGF and activate Erk 1/2-Elk1 signal path. After interference by siRNA, ERK1/2 pathway was blocked in cells, and the expression of MMP-2/9 was down-regulated. ERK1/2 specific blocker U0126 blocked ERK phosphorylation, and it could down-regulate the expression of MMP-2/9.
The results showed that the estrogen can increase the expression of VEGF, and thus activate ERK1/2 pathway to induce MMP-2/9 expression.
研究雌激素对无排卵性功能失调性子宫出血（ADUB）的影响。
培养海南黎族女性原代子宫内膜上皮细胞，通过明胶酶谱分析测定明胶酶的水解活性。分别阻断细胞 mRNA 和蛋白质合成，以确定 MMP-2/9 的表达增加是否是由雌激素诱导的。用 siRNA 阻断 VEGF 的表达。用 Western blot 分析检测经各种因素处理后原代子宫上皮细胞中 MMP-9、VEGF、总 Erk 和磷酸化 Erk 的表达。通过实时 RT-PCR 测量细胞 MMP-2/9mRNA 水平。
ADUB 患者的子宫内膜中 MMP2/9 的活性和表达增加。雌激素可上调 VEGF 的表达并激活 Erk 1/2-Elk1 信号通路。用 siRNA 干扰后，细胞中 ERK1/2 通路被阻断，MMP-2/9 的表达下调。ERK1/2 特异性阻滞剂 U0126 阻断 ERK 磷酸化，可下调 MMP-2/9 的表达。
结果表明，雌激素可增加 VEGF 的表达，从而激活 ERK1/2 通路诱导 MMP-2/9 的表达。
