人纤维蛋白原α链（FGA）在子宫内膜异位症中作用及其机制的探索

子宫内膜异位症(EM)发病机理有多个学说，有研究认为内膜碎片须经粘附、侵袭和血管形成才可在异位种植形成病灶。我中心前期发现人纤维蛋白原α链（FGA）在患者血清中上调；经验证FGA在患者子宫内膜中表达也升高，且间质表达强。FGA含RGD序列，是细胞粘附分子的一种，有介导细胞粘附迁移的功能，文献提示高水平FGA小鼠更易形成异位病灶，外源添加RGD抑制肽可抑制其形成；据报道与细胞粘附相关的PI3K和MAPK等信号通路在EM中过度激活。据此假设：FGA可能通过某种信号通路调节多种细胞粘附分子的表达，促进内膜细胞的粘附迁移，进而影响EM的发生发展。本研究拟在前期建立的EM永生化细胞系的基础上构建FGA敲降/敲除的细胞模型，鉴定后研究细胞生物学特性的改变；探索相关的细胞粘附分子及可能的信号通路，观察对动物模型中病灶形成的影响；应用Lnc-RNA、基因、蛋白等芯片初筛上下游分子，为EM诊治提供新的思路。

Endometriosis (EM) is a common gynecological diseases, of which pathogenesis is not clear. It is reported that endometrial fragments need to go through adhesion, invasion and angiogenesis before planting ectopic lesion formation. Our center has found increasing level of fibrinogen α chain (FGA) in serum of EM patients. We have proven that FGA expression was also elevated in patients’ endometrium, especially in stroma. FGA protein, as a cell adhesion molecule, contains the RGD sequence, and could mediate cell migration and adhesion. A study showed mice with high level of FGA were more easily to form ectopic focus, which could be inhibited by RGD inhibition peptides. Accordingly hypothesis: FGA protein may regulate the expression of some cell adhesion molecules through certain signaling pathway, and promote migration and adherence function of endometrial cells, thereby affecting the development of the EM. In this study, we will establish FGA knock-down/out cell models on the basis of immortalized EM-derived cell line established by our center. Identify the biological properties of established cell models. Explore related extracellular adhesion molecules and signaling pathway. Observe success rate of each animal modele. Screen upstream and downstream targets by Lnc-RNA, gene and protein chips and provide new theoretical basis for the diagnosis and treatment of EM.