Gene Regulation And Function Of Basement Membranes

基底膜是薄的细胞外基质，将细胞（如内皮细胞、上皮细胞、肌肉细胞和神经细胞）与邻近的基质分开。基底膜是发育过程中最先出现的细胞外基质，在发育和组织修复过程中被降解和再生。它们不仅为细胞和细胞层提供支架，而且在影响细胞粘附、迁移、增殖和分化的形态发生中起着重要作用。此外，基底膜在血管中为蛋白质的通过和转移性肿瘤细胞的侵袭提供了主要屏障。基底膜的厚度和组成在不同的组织中是不同的，表明其具有组织特异性的功能。基底膜的主要分子是胶原IV、层粘连蛋白、纤维蛋白和氮素/内动蛋白，它们相互作用形成超分子结构。最近，层粘连蛋白和IV型胶原亚基的遗传多样性已经被发现，并且这些分子的一个大家族的存在已经被证明。我们的主要目标是确定基底膜组分的特定功能，研究结构和功能关系，阐明它们的调节机制，并描述发育和疾病中的相关蛋白质相互作用。我们的工作也集中在建立动物模型来研究基底膜成分在发育和疾病中的功能，并为与基底膜相关的疾病创造治疗试剂。我们还发现了层粘连蛋白上具有许多生物活性的生物活性位点，如促进细胞粘附、迁移和神经突生长，并影响肿瘤细胞的转移活性。这些研究旨在开发用于诊断和治疗应用的试剂。

Basement membranes are thin extracellular matrices that separate cells, such as endothelial, epithelial, muscular, and neural cells, from their adjacent stroma. Basement membranes are the first extracellular matrix to appear in development and are degraded and regenerated during development and tissue repair. They not only provide the scaffold for cells and cell layers, but they also have an essential role in morphogenesis that affects cell adhesion, migration, proliferation, and differentiation. Additionally, basement membranes provide major barriers in blood vessels to the passage of proteins and invasion by metastatic tumor cells. The thickness and components of basement membranes are different in various tissues, suggesting tissue-specific functions. The major molecules in basement membranes are collagen IV, laminin, perlecan, and nidogen/entactin, which interact with each other to form the supramolecular structure. Recently, genetic diversity in the subunits of laminin and type IV collagen has been found and the existence of a large family of these molecules has been demonstrated. Our primary objectives have been to identify the specific functions of basement membrane components, to study the structure and function relationships, to elucidate the mechanisms by which they are regulated, and to describe related protein interactions in development and diseases. Our effort has also focused on establishing animal models to study functions of basement membrane components in development and disease and on creating therapeutic reagents for diseases associated with basement membranes. We have also identified bioactive sites on laminin that have a number of biological activities, such as promoting cell adhesion, migration, and neurite outgrowth, and affecting metastatic activity of tumor cells. These studies are aimed towards developing reagents useful for diagnostic and therapeutic applications.