Pan H, Zhang P, Li J-R, Wang H, Jin M-F, Feng C, Huang H-F
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910 Hengshan Road, Shanghai 200030, China.
Curr Mol Med. 2016;16(3):266-75. doi: 10.2174/1566524016666160225153454.
Endometriosis is a frequent gynecological disease associated with severe pain and infertility. Although its dependency on estrogen is well recognized, the molecular mechanism along the estrogenic pathway has not been fully understood. This study investigates the effect of 17β-estradiol (E2) on human endometrial stromal cell (HESC) invasion and the role of c-fos and matrix metalloproteinase-9 (MMP-9) in mediating the biological function of 17β-E2. It is found that 17β-E2 promotes not only HESC invasion, but also c-fos and MMP-9 expression in HESC. Further experiments demonstrate that the estrogen receptor inhibitor ICI 182780 and siRNA-mediated c-fos or MMP-9 knockdown are able to block the effect of 17β-E2 on HESC invasion. Moreover, siRNA-mediated c-fos knockdown suppresses the effect of 17β-E2 on MMP-9 expression. Our results indicate that 17β-E2-induced HESC invasion is dependent on c-fos-mediated MMP-9 expression. These findings facilitate our understanding on the pathogenesis of endometriosis and may provide data potentially useful for the development of new treatment modalities for better management of endometriosis.
子宫内膜异位症是一种常见的妇科疾病，与严重疼痛和不孕相关。尽管其对雌激素的依赖性已得到充分认识，但雌激素信号通路的分子机制尚未完全阐明。本研究探讨了17β-雌二醇（E2）对人子宫内膜基质细胞（HESC）侵袭的影响，以及c-fos和基质金属蛋白酶-9（MMP-9）在介导17β-E2生物学功能中的作用。研究发现，17β-E2不仅促进HESC侵袭，还促进HESC中c-fos和MMP-9的表达。进一步实验表明，雌激素受体抑制剂ICI 182780以及siRNA介导的c-fos或MMP-9基因敲低能够阻断17β-E2对HESC侵袭的影响。此外，siRNA介导的c-fos基因敲低抑制了17β-E2对MMP-9表达的影响。我们的结果表明，17β-E2诱导的HESC侵袭依赖于c-fos介导的MMP-9表达。这些发现有助于我们理解子宫内膜异位症的发病机制，并可能为开发更好管理子宫内膜异位症的新治疗方法提供潜在有用的数据。
