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REGULATION OF DECIDUAL CELL TISSUE FACTOR EXPRESSION

蜕膜细胞组织因子表达的调节

基本信息

批准号：
2403280
负责人：
CHARLES JOSEPH LOCKWOOD
金额：
$ 5.92万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-09-01 至 1999-08-31
项目状态：
已结题

项目摘要

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.

人类子宫内膜避免滋养层血管浸润时出血，但矛盾的是，导致尿道相关的血管破裂，目前尚不清楚。同样地，关于潜在的致病机制的信息很少，与不良产科结局相关的异常子宫出血，不排卵和避孕治疗。这个基本的难题生殖生物学是通过我们的假设，基质细胞通过增加表达促进子宫内膜止血有效的促凝血组织因子（TF），黄体期的促孕刺激，以及月经通过减少TF的表达，以响应孕酮的撤除，在黄体期结束时。该假设将通过以下方式进行检验：来自周期性子宫内膜的基质细胞和来自第一次周期性子宫内膜的蜕膜细胞孕三个月子宫内膜检查：l）孕激素的影响和胰蛋白酶拮抗剂对TF合成和降解速率的影响 m-RNA和蛋白质在基质细胞单层，以及这些影响是否涉及内分泌或自分泌因素的调解; 2）影响对孕激素调节的间质细胞TF表达的影响外源性和内源性生长因子的单细胞膜已经暗示在女性的蜕膜化反应中; 3）细胞的作用- 细胞外基质（ECM）在调节胰蛋白酶和生长中的相互作用因子调节基质细胞和蜕膜细胞中TF的表达;和4）细胞-细胞相互作用在调节胰高血糖素，生长因子，和ECM调节的TF表达在基质细胞和蜕膜细胞中的共同作用，子宫内膜腺细胞-基质细胞和滋养层细胞的培养细胞-蜕膜细胞。实验结果将有助于解剖与蜕膜化相关的TF表达调节机制体外将这些结果外推到体内状态，阐明蜕膜细胞相关TF在子宫内膜异位症中的重要性，月经期和月经期。一旦生理蜕膜细胞TF的作用是建立新的诊断和治疗在这些过程中处理异常出血的方法可以是预计将遵循。