REGULATION OF DECIDUAL CELL TISSUE FACTOR EXPRESSION

蜕膜细胞组织因子表达的调节

• 批准号: 2201956
• 负责人: CHARLES JOSEPH LOCKWOOD
• 金额: $ 13.83万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2201956
• 关键词: RNA biosynthesis; SDS polyacrylamide gel electrophoresis; cell cell interaction; decidua; endometrium; enzyme linked immunosorbent assay; extracellular matrix; hormone regulation /control mechanism; human tissue; immunoprecipitation; in situ hybridization; light microscopy; menstrual cycle; messenger RNA; mixed tissue /cell culture; northern blottings; nuclear runoff assay; progestins; protein biosynthesis; receptor expression; transforming growth factors; western blottings

The physiological mechanisms whereby the human endometrium avoids hemorrhage during trophoblastic vascular invasion, yet paradoxically permits menstrual-related vascular disruption, are unknown. Similarly, there is a paucity of information on the pathogenic mechanisms underlying abnormal uterine bleeding associated with adverse obstetrical outcomes, anovulation and contraceptive therapy. This fundamental conundrum in reproductive biology is addressed through our hypothesis that decidualized stromal cells contribute to endometrial hemostasis by increased expression of the potent procoagulant tissue factor (TF) in response to progestational stimulation during the luteal phase, and to menstruation via decreased TF expression in response to the withdrawal of progesterone at the end of the luteal phase. This hypothesis will be tested using stromal cells from cycling endometrium and decidual cells from first trimester pregnant endometrium to examine: l) the effects of progestins and progestin antagonists on the rates of synthesis and degradation of TF m-RNA and protein in stromal cell monolayers, and whether these effects involve mediation of intracrine or autocrine factors; 2) the influence exerted on progestin-regulated TF expression in the stromal cell monolayers by exogenous and endogenous growth factors already implicated in the decidualization reaction in women; 3) the role of cell- extracellular matrix (ECM) interactions in modulating progestin and growth factor regulated TF expression in stromal cells and decidual cells; and 4) the role of cell-cell interactions in modulating progestin, growth factor, and ECM-regulated TF expression in stromal cells and decidual cells in co- cultures of endometrial glandular cells-stromal cells and trophoblastic cells-decidual cells. The experimental results will aid in the dissection of mechanisms regulating TF expression associated with decidualization in vitro. Extrapolation of these results to the in vivo state should elucidate the importance of decidual cell-associated TF in peri- implantational events, and during menstruation. Once the physiological role of decidual cell TF is established new diagnostic and therapeutic approaches to deal with abnormal bleeding during these processes can be expected to follow.

人子宫内膜避免的生理机制 滋养细胞血管入侵期间出血，但自相矛盾的是 允许月经相关的血管破坏是未知的。相似地， 关于致病机制的信息很少 与不良产科结果相关的子宫出血异常， 电炉和避孕疗法。这个基本的难题 生殖生物学是通过我们的假设解决的 基质细胞通过增加表达导致子宫内膜止血 响应有效的凝结组织因子（TF） 黄体期间的摄取刺激和月经 通过响应孕酮的响应降低TF表达 在黄体阶段结束时。该假设将使用 来自第一循环子宫内膜和dec骨细胞的基质细胞。 孕期怀孕子宫内膜检查：l）孕激素的作用 TF的合成速率和降解速率和孕激素拮抗剂 基质细胞单层中的M-RNA和蛋白质，以及这些影响是否 涉及内部或自分泌因素的介导； 2）影响 施加在基质细胞中的孕激素调节的TF表达上 由外源和内源性生长因子与已经牵涉的外源和内源性生长因子 在妇女的c否反应中； 3）细胞的作用 调节孕激素和生长中的细胞外基质（ECM）相互作用 因子调节基质细胞和codi骨细胞中的TF表达；和4） 细胞 - 细胞相互作用在调节孕激素，生长因子， 和ECM调节的TF表达在共同细胞和dec骨细胞中 子宫内膜腺细胞的培养物和滋养细胞的培养 细胞 - 白细胞。实验结果将有助于解剖 调节与deDialization相关的TF表达的机制 体外。将这些结果推送到体内状态应 阐明决定型细胞相关的TF在周日的重要性 植入事件以及月经期间。一旦生理 确定了deciDual细胞TF的作用，建立了新的诊断和治疗性 在这些过程中处理异常出血的方法可能是 预计将跟随。