METALLOPROTEINASE/DISINTEGRIN FUNCTION IN ENDOMETRIUM

子宫内膜中的金属蛋白酶/解整合素功能

• 批准号: 6588501
• 负责人: LOREN H HOFFMAN
• 金额: $ 17.42万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6588501
• 关键词: athymic mouse; cell adhesion; cell adhesion molecules; cell cell interaction; cell fusion; clinical research; cooperative study; cytoskeletal proteins; embryo implantation; endometriosis; endometrium; female; gene expression; human tissue; in situ hybridization; integrins; laboratory rabbit; ligands; metalloendopeptidases; posttranslational modifications; protein localization; protein structure function; trophoblast; western blottings; women's health

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.

子宫内膜上皮细胞在发育过程中发生了剧烈的重塑， 围着床期。这些变化包括细胞-细胞 细胞-基质相互作用中的粘附，改变的顶-底极性， 在某些物种中，细胞与细胞的融合。我们记录了 编码跨膜蛋白rbMDC 9的mRNA的表达， 亚当斯基因家族的潜在细胞结合，细胞基质 相互作用和融合特性。RbMDC 9表达上调 在植入激素准备期间，在兔子宫内膜中，和 胚泡进一步增强表达。初步证据 表明在小鼠和人类子宫中有类似的上调。我们将测试 兔中MDC 9作为整合素结合蛋白的假设 上皮细胞之间的粘附分子，并且在这样做时， 在连接和细胞骨架蛋白的重新分布中起作用。 此外，我们假设亚当斯家族蛋白参与了 细胞-基质相互作用和相邻上皮细胞之间的融合 细胞之间以及滋养层和上皮细胞之间， 以及在子宫内膜异位附着和侵袭中的作用 子宫内膜异位症该项目的目的将是1），以确定是否域 特异性靶向和翻译后加工调节 上皮细胞rbMDC 9在围着床期的作用 子宫内膜，2）以确定是否需要rbMDC 9配体相互作用 对于子宫上皮连接或细胞骨架蛋白修饰 3）确定rbMDC 9在移植过程中的功能， 增殖特异性细胞-细胞粘附和/或融合过程，和 确定其处理的表达是否受到以下方面的监管： 体外胚泡，和4）确定MDC 9是否在 子宫内膜周期特异性模式 目的探讨子宫内膜异位症的发病机制，分析其在子宫内膜异位症发病中的调控作用。 在实验性子宫内膜异位症模型中观察异位内膜的粘附和侵袭 子宫内膜异位症