METALLOPROTEINASE/DISINTEGRIN FUNCTION IN ENDOMETRIUM

子宫内膜上皮细胞在月经周期中经历戏剧性的重塑。 围植入期。这种变化包括细胞-细胞的改变 粘连，在细胞-基质相互作用中，修改的尖端-底端极性， 而且，在某些物种中，细胞与细胞融合。我们已经记录了 成员rbMDC9跨膜蛋白编码基因的表达 具有潜在细胞结合、细胞基质的亚当斯基因家族 相互作用和融合特性。RbMDC9表达上调 在植入激素准备过程中的兔子宫内膜，以及 胚泡进一步增强了表达。初步证据 在小鼠和人的子宫中也有类似的上调。我们将测试 兔MDC9作为整合素结合因子的假说 上皮细胞之间的黏附分子，在这样做的同时，还 在连接蛋白和细胞骨架蛋白的重新分布中的作用。 此外，我们假设亚当斯家族蛋白参与了 细胞-基质相互作用及相邻上皮细胞间的融合 在着床过程中滋养细胞和上皮细胞之间， 在子宫内膜组织的异位附着和侵袭中 子宫内膜异位症。该项目的目的将是1)确定是否域 特定靶向和翻译后加工调节 上皮细胞rbMDC9在围着床期的作用 子宫内膜，2)确定是否需要rbMDC9配体相互作用 用于子宫上皮连接或细胞骨架蛋白修饰 在植入过程中，3)明确rbMDC9在体内的功能 植入特有的细胞-细胞黏附和/或融合过程，以及 确定其加工表达是否受 4)以确定MDC9是否在 子宫内膜异位基因在子宫内膜中的表达 并分析其在子宫内膜异位症中的调节作用和可能的作用。 异位子宫内膜黏附和侵袭的实验研究 子宫内膜异位症。

Endometrial epithelial cells undergo dramatic remodeling during the peri-implantation period. Such changes include alterations in cell-cell adhesions, in cell-matrix interactions, modified apical-basal polarity, and, in some species, cell-cell fusion. We have documented the expression of an mRNA encoding a transmembrane protein rbMDC9, a member of the ADAMs gene family with potential cell binding, cell-matrix interactions and fusogenic properties. RbMDC9 expression is up-regulated in rabbit endometrium during hormonal preparation for implantation, and expression is further augmented by blastocysts. Preliminary evidence suggests a similar up-regulation in mouse and human uteri. We will test the hypothesis that MDC9 in rabbits serve as an integrin-binding adhesion molecule between epithelial cells and, in doing so, also functions in the redistribution of junction and cytoskeletal proteins. Furthermore, we hypothesize that ADAMs family proteins participate in cell-matrix interactions and in the fusions between adjacent epithelial cells and between trophoblast and epithelial cells during implantation, and in the ectopic attachment and invasion of endometrial tissue during endometriosis. Aim of the project will be 1) to determine if domain specific-targeting and post-translational processing regulate the function of epithelial cell rbMDC9 in peri-implantation-stage endometrium, 2) to determine if rbMDC9 ligand interactions are required for uterine epithelial junction or cytoskeletal protein modifications during implantation, 3) to define the function of rbMDC9 in implantation-specific cell-cell adhesion and/or fusion processes, and determine whether its expression of processing are regulated by blastocysts in vitro, and 4) to determine if MDC9 is expressed in a cycle-specific pattern in endometrium of women with and without endometriosis, and to analyze its regulation and potential roles in the adhesion and invasion of ectopic endometrium in an experimental model of endometriosis.