REGULATION OF CELL DIFFERENTATION DURING DECIDUALIZATION

蜕化过程中细胞分化的调控

• 批准号: 6233083
• 负责人: ZUZANA STRAKOVA
• 金额: $ 7.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-06 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6233083
• 关键词: Primates; actins; baboons; binding proteins; biological signal transduction; cell differentiation; cytoskeleton; decidua; enzyme activity; enzyme induction /repression; enzyme inhibitors; extracellular matrix; fibroblasts; human tissue; insulinlike growth factor; integrins; interleukin 1; polymerase chain reaction; pregnancy; prostaglandin endoperoxide synthase; pseudopregnancy; retinoate; steroid hormone; stromelysin; tissue /cell culture; western blottings

One of the most remarkable processes associated with the establishment of pregnancy in the primate is the process of decidualization. This transformation of a stromal fibroblast to a fully differentiated decidual cell is required for implantation and embryo survival in early pregnancy. Although the morphological and biochemical characteristics of the primate decidual cell have been extensively studied, the precise regulation and activation of signaling pathways required for this transformation have yet to be elucidated. Decidualization in baboon consists from the initial proliferative phase, followed by a differentiation phase The differentiation phase is characterized by the down-regulation of alpha-smooth muscle actin (alpha-smooth muscle actin (alpha-SMA) and expression of insulin-like growth factor binding protein-1 (IGFBP-1), the biochemical marker of decidualization in the baboon. This phase requires the presence of conceptus in vivo or stimulation with cAMP or interleukin-1beta (IL-1beta) in presence of hormones in vitro. This application focuses on the potential signaling pathways that are activated by IL-1beta, an important cytokine at maternal-fetal interphase. Decidualization requires active remodeling of the stromal cell and we will determine in specific aim 1 the role of matrix metalloproteinase-3 (MMP- 3) in this process. The role of the steroid hormones in inhibit excessive MMP-3 activity through retinoic acid will be addressed in Specific aim 2. The proposed studies will enable us to obtain basic data under defined in vitro cell culture conditions regarding the regulatory and signaling pathways at fetal/maternal interface during implantation. These results will form the basis for a future R01 application. The ultimate goal of our studies is a thorough understanding of the cellular and molecular changes that occur during implantation. We anticipate that our ongoing studies will contribute to find therapies to treat endometrial dysfunctions associated with infertility, habitual abortions and/or insufficient placental development.

在灵长类动物中建立怀孕的最引人注目的过程之一是义词化过程。在怀孕初期，需要将基质成纤维细胞向完全分化的决切细胞转化。尽管已广泛研究了灵长类动物判断细胞的形态和生化特征，但这种转化所需的信号传导途径的精确调控和激活尚未阐明。 Decidualization in baboon consists from the initial proliferative phase, followed by a differentiation phase The differentiation phase is characterized by the down-regulation of alpha-smooth muscle actin (alpha-smooth muscle actin (alpha-SMA) and expression of insulin-like growth factor binding protein-1 (IGFBP-1), the biochemical marker of decidualization in the baboon. This phase requires the presence of conceptus in在体外存在激素的cAMP或INTRUUIKIN-1BETA（IL-1BETA）的体内或刺激。该应用集中在IL-1Beta激活的潜在信号通路上，IL-1Beta是一种重要的细胞因子，这是一种在母体范围内的固定剂。 3）在这种过程中，在特定目标中抑制通过视黄酸抑制过度的MMP-3活性。提议的研究将使我们能够在体外细胞培养条件下获得有关胎儿/孕妇在植入过程中的详细群体的基本数据。植入过程中发生的变化。