REGULATION OF DECIDUAL CELL TISSUE FACTOR EXPRESSION

蜕膜细胞组织因子表达的调节

• 批准号: 3470579
• 负责人: CHARLES JOSEPH LOCKWOOD
• 金额: $ 13.45万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 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/3470579
• 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.

人类子宫内膜避免的生理机制 滋养层血管侵犯期间出血，但矛盾的是 是否会导致月经相关的血管破坏，目前尚不清楚。相似地， 关于潜在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， 停止排卵和避孕治疗。这个基本难题在 生殖生物学是通过我们的假设来解决的，即蜕膜化 基质细胞通过增加表达促进子宫内膜止血 强效促凝血组织因子 (TF) 的反应 黄体期和月经期间的孕激素刺激 通过响应黄体酮的撤退而减少 TF 表达 在黄体期结束时。该假设将使用以下方法进行检验 来自循环子宫内膜的基质细胞和来自第一次的蜕膜细胞 孕晚期子宫内膜检查： l) 孕激素的影响 和孕激素拮抗剂对 TF 合成和降解速率的影响 基质细胞单层中的 mRNA 和蛋白质，以及这些影响是否 涉及内分泌或自分泌因素的介导； 2）影响 影响基质细胞中孕激素调节的 TF 表达 已经涉及的外源性和内源性生长因子的单层细胞 女性的蜕膜化反应； 3）细胞的作用- 细胞外基质 (ECM) 相互作用在调节孕激素和生长中的作用 因子调节基质细胞和蜕膜细胞中的 TF 表达；和 4) 细胞间相互作用在调节孕激素、生长因子、 和 ECM 调节的基质细胞和蜕膜细胞中的 TF 表达 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 表达调节机制的研究 体外。将这些结果外推到体内状态应该 阐明蜕膜细胞相关 TF 在围周期的重要性 着床事件和月经期间。一旦生理 蜕膜细胞 TF 的作用已确立 新的诊断和治疗方法 处理这些过程中异常出血的方法可以是 预计将遵循。