Collagen XVIII in Corneal Neovascularization

XVIII 胶原蛋白在角膜新生血管中的作用

• 批准号: 7105535
• 负责人: JIN-HONG CHANG
• 金额: $ 26.49万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105535
• 关键词: angiogenesis; cell growth regulation; cell migration; cell proliferation; collagen; cornea; genetically modified animals; histogenesis; laboratory mouse; metalloendopeptidases; pathologic process; protein localization; protein structure function; vascular endothelium; wound healing

DESCRIPTION (provided by applicant): Background: Corneal neovascularization is a major cause of blindness worldwide. The objective of our research is to identify the role of collagen XVIII and its proteolytic fragments in corneal neovascularization. Our laboratory has found that MMP-7 cleaves corneal and recombinant collagen XVIII to generate a 28 kDa fragment which may regulate corneal neovascularization during corneal wound healing. Hypothesis: Activated MMP-7 in cornea may contribute to the production of endostatin and endostatin-spanning fragments, which inhibit corneal neovascularization. Specific Aims: A. To determine the distribution of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in the cornea in vivo and in vitro. B. To characterize the function of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in vascular endothelial cell proliferation, migration, and tube formation in vitro. C. To characterize the role of endostatin and MMP-7-derived proteolytic fragment of collagen XVIII in corneal neovascularization in vivo. Significance: Understanding the mechanisms that maintain corneal avascularity may allow us to prevent blindness caused by corneal neovascularization. The study of endostatin and MMP-7 in the cornea may provide valuable information about their possible clinical significance in corneal neovascularization and wound healing.

描述（由申请人提供）：背景：角膜新血管化是全球失明的主要原因。我们研究的目的是确定胶原蛋白XVIII及其蛋白水解片段在角膜新血管形成中的作用。我们的实验室发现，MMP-7裂解角膜和重组胶原蛋白XVIII产生28 kDa碎片，可能在角膜伤口愈合过程中调节角膜新生血管化。 假设：角膜中激活的MMP-7可能有助于抑制角膜新血管形成的内静脉素和跨抑制蛋白的片段的产生。 具体目的： 答：确定体内和体外角膜中胶原蛋白XVIII的内接和MMP-7衍生的蛋白水解片段的分布。 B.表征在血管内皮细胞增殖，迁移和管子形成中，胶原蛋白XVIII的内骨和MMP-7衍生的蛋白水解片段的功能。 C.表征胶原蛋白XVIII在体内角膜新生血管中的胶原蛋白的内接和MMP-7衍生的蛋白水解片段的作用。 意义：了解维持角膜血管的机制可能会使我们能够防止角膜新血管形成引起的失明。角膜中内抑素和MMP-7的研究可能会提供有关其在角膜新血管形成和伤口愈合中可能临床意义的宝贵信息。