Estrogen up-regulates MMP2/9 expression in endometrial epithelial cell via VEGF-ERK1/2 pathway

Objective: To study the effect of estrogen on anovulatory dysfunctional uterine bleeding (ADUB). Methods: 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-219 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 primly uterine epithelial cells was detected by Western blotting analysis. Cell MMP-2/9mRNA levels was measured by real-time RT-PCR. Results: 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. Conclusions: The results showed that the estrogen can increase the expression of VEGF, and thus activate ERK1/2 pathway to induce MMP-2/9 expression.