Role Of Extracellular Matrix In Cell Differentiation And

细胞外基质在细胞分化中的作用

• 批准号: 6673921
• 负责人: HYNDA K KLEINMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6673921
• 关键词: angiogenesis; basement membrane; cell adhesion; cell differentiation; cell growth regulation; cell migration; extracellular matrix; extracellular matrix proteins; gene induction /repression; human tissue; laminin; neurons; salivary glands; synthetic peptide; tissue /cell culture; vascular endothelium

The extracellular matrix has been found to be important in embryogenesis and in tissue repair. From in vitro studies using purified components, a better understanding of how cells adhere, migrate, proliferate, and differentiate in response to tissue and cell- specific matrix molecules has been established. We have found that the basement membrane, the extracellular matrix which underlies all epithelial cells and endothelial cells and surrounds nerve cells, promotes cell differentiation in vitro. When cultured on basement membrane, endothelial cells form capillary-like structures with a lumen, chondrocytes form cartilage, salivary cells form glands, etc. Our goal is to define the molecular and cellular events involved in this process. Our approach has been (1) to identify the biologically active matrix components, with respect to cell adhesion, migration, proliferation and differentiation, (2) localize active sites on the matrix component with synthetic peptides, (3) identify and characterize cellular receptors, (4) gain an understanding of the intracellular events involved in the biological response, and (5) identify genes induced by the extracellular matrix. We work in several in vitro model systems including primary and established tumor cells, endothelial cells, and salivary glands and cells. We have used the endothelial cell tube assays in vitro and in vivo angiogenesis assays to define molecules which regulate vessel formation in development and disease. Our goal is to discover new angiogenic regulators. Salivary gland cells and developing glands in vitro have been used to define factors important to gland development and function. Our goal is to understand how the extracellular matrix regulates tissue formation, repair, and certain pathological processes. We hope to develop both therapeutic and diagnostic agents.

细胞外基质已被发现在胚胎发育和组织修复中起重要作用。通过使用纯化成分的体外研究，对细胞如何黏附、迁移、增殖和分化以响应组织和细胞特定的基质分子已经有了更好的理解。我们发现基底膜在体外促进细胞分化，基底膜是细胞外基质，位于所有上皮细胞和内皮细胞之下，包围着神经细胞。当培养在基底膜上时，内皮细胞形成带腔的毛细血管样结构，软骨细胞形成软骨，唾液细胞形成腺体等。我们的目标是确定参与这一过程的分子和细胞事件。我们的方法是(1)识别与细胞黏附、迁移、增殖和分化有关的生物活性基质成分，(2)用合成肽定位基质成分上的活性部位，(3)识别和表征细胞受体，(4)了解参与生物反应的细胞内事件，以及(5)识别由细胞外基质诱导的基因。我们在几个体外模型系统中工作，包括原代和已建立的肿瘤细胞、内皮细胞以及唾液腺和细胞。我们使用了体外血管内皮细胞管实验和体内血管生成实验来定义在发育和疾病过程中调节血管形成的分子。我们的目标是发现新的血管生成调节剂。唾液腺细胞和体外发育的腺体已被用来定义对腺发育和功能重要的因素。我们的目标是了解细胞外基质如何调节组织的形成、修复和某些病理过程。我们希望同时开发治疗和诊断试剂。