TFF-petides and their mechanisms of action during cell migration

三叶因子（TFFs）代表最近在非洲爪蟾和非洲蟾蜍中鉴定的分泌多肽家族，其在成年哺乳动物生物体中主要在胃肠道组织中表达。TFF功能的研究已经确定TFF作为运动原在上皮恢复的早期过程中起作用，当细胞从受损区域的边缘快速迁移到裸露区域以重建上皮连续性时。在本项目中，应检查三叶肽诱导迁移的细胞和分子机制。首先，将通过生化分析和免疫荧光显微镜分析TFF在迁移过程中对钙粘蛋白-连环蛋白粘附复合物的影响。第二，它应解决顶端糖蛋白，如DF 3/MUC 1是否发挥TFF受体的作用，以及TFF与这些糖蛋白的结合是否是钙粘蛋白-连环蛋白系统的调节环节。此外，三叶肽的运动原活性是否也是由基底外侧受体介导的还有待进一步研究。第三，采用差异cDNA分析（cDNA阵列）和高分辨率2D-凝胶电泳，TFF诱导的基因表达和信号蛋白的翻译后修饰的变化应被鉴定和测试它们在诱导细胞迁移中的相关性。

Trefoil factors (TFFs) represent a family of secreted polypeptides recently identified in mammalians and Xenopus that in adult mammalian organisms are expressed mainly in tissues of the gastrointestinal tract. Studies of TFF function have identified TFFs as motogens acting in early processes of epithelial restitution when cells rapidly migrate from the margins of the damaged region over the denuded area to reestablish epithelial continuity. In this project the cellular and molecular mechanisms responsible for the induction of migration by trefoil peptides shall be examined. First, the influence of TFFs on the cadherin-catenin adhesion complex during migration will be analyzed by biochemical analysis and immunofluorescence microscopy. Second, it shall be adressed whether apical glycoproteins such as DF3/MUC1 play a role as TFF receptors and whether binding of TFF to these glycoproteins is a regulatory link to the cadherin-catenin system. Furthermore, it shall be adressed whether the motogenic activity of trefoil peptides is also mediated by basolateral receptors. Third, employing differential cDNA analysis (cDNA arrays) and high-resolution 2D-gelelectrophoresis, TFF induced changes in gene expression and posttranslational modifications of signaling proteins shall be identified and tested for their relevance in induction of cell migration.