Gene Regulation And Function Of Basement Membranes
基底膜的基因调控和功能
基本信息
- 批准号:6501178
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
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.
基底膜是薄的细胞外基质,其将细胞(如内皮细胞、上皮细胞、肌肉细胞和神经细胞)与其相邻的基质分开。基底膜是发育中出现的第一个细胞外基质,在发育和组织修复过程中降解和再生。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重要作用。此外,基底膜在血管中提供主要屏障以阻止蛋白质通过和转移性肿瘤细胞的侵袭。基底膜的厚度和成分在不同组织中是不同的,提示组织特异性功能。基底膜中的主要分子是IV型胶原、层粘连蛋白、串珠素和巢蛋白/巢蛋白,它们彼此相互作用形成超分子结构。最近,已发现层粘连蛋白和IV型胶原蛋白亚基的遗传多样性,并且已证明存在这些分子的大家族。我们的主要目标是确定基底膜成分的特定功能,研究结构和功能的关系,阐明它们被调节的机制,并描述发育和疾病中相关的蛋白质相互作用。我们的努力还集中在建立动物模型,以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。我们还确定了层粘连蛋白上的生物活性位点,这些位点具有许多生物活性,例如促进细胞粘附、迁移和神经突生长,以及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。
项目成果
期刊论文数量(0)
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Yoshihiko Yamada其他文献
Yoshihiko Yamada的其他文献
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{{ truncateString('Yoshihiko Yamada', 18)}}的其他基金
Basement Membranes and Associated Protein Factors In Development and Disease
发育和疾病中的基底膜和相关蛋白质因子
- 批准号:
8553324 - 财政年份:
- 资助金额:
-- - 项目类别:
Basement Membranes and Associated Protein Factors In Development and Disease
发育和疾病中的基底膜和相关蛋白质因子
- 批准号:
7593363 - 财政年份:
- 资助金额:
-- - 项目类别:
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