VEGFR2 Modulates Corneal Angiogenesis and Lymphangiogenesis

VEGFR2 调节角膜血管生成和淋巴管生成

• 批准号: 8702186
• 负责人: JIN-HONG CHANG
• 金额: $ 19.54万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702186
• 关键词: Alkalies; Binding; Blindness; Blood Vessels; Breeding; Burn injury; Cell Proliferation; Cells; Clinical; Cornea; Corneal Injury; Corneal Neovascularization; Disease; Endothelial Cells; Epithelial; Equilibrium; Experimental Models; Eye; Goals; Green Fluorescent Proteins; Image; In Vitro; Individual; Infection; Knock-out; Knockout Mice; Lead; Ligands; Limbus Corneae; Lymphangiogenesis; Lymphatic; Lymphatic vessel; Maintenance; Mediating; Membrane; Methods; Modeling; Molecular; Mus; Neoplasm Metastasis; Play; Procedures; Process; Production; Protein Isoforms; Regulation; Relative (related person); Research; Role; Signal Transduction; Therapeutic; Time; Transplantation; Tube; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factor Receptor-3; Vascular Endothelial Growth Factors; Vascularization; angiogenesis; cadherin 5; cell motility; design; dimer; in vivo; injured; limbal; migration; neovascularization; novel therapeutic intervention; prevent; public health relevance; receptor; receptor binding; research study; response; spatiotemporal; tumor growth

DESCRIPTION (provided by applicant): Corneal neovascularization (NV) is a common, disabling condition and a major cause of blindness that can follow corneal injury or infection. Our long term goal is to characterize the role of VEGF receptors in the two central corneal vascularization processes, vascular angiogenesis (VA) and lymphangiogenesis (LA). The involvement of the epithelial, soluble form of VEGFR-2 (sVEGFR-2) in LA has been well characterized. However, the role of membrane- bound, vascular VEGFR-2 (mbVEGFR-2) in corneal VA and LA has not. These proposed experiments are designed to characterize the potential angiogenic and lymphangiogenic roles of the membrane bound isoform of VEGFR-2. We propose the hypothesis that vascular mbVEGFR2 may have distinct roles, separate from those of VEGFR1 or VEGFR3, in response to induction by VEGF-A (towards VA) or VEGF-C (towards LA) in corneal angiogenesis/ lymphangiogenesis. Two specific aims have been proposed to characterize the role of VEGFR- 2 in corneal angiogenesis and lymphangiogenesis. Aim A. Use inducible, conditional knockout mouse lines to determine whether mbVEGFR2 maintains a counterbalanced relationship with sVEGFR1 and sVEGFR2 in the cornea. Aim B. Characterize the individual roles of pro- angiogenic agents on VEGFR activity and VA/LA initiation, progression, and maintenance. SIGNIFICANCE: The endothelial receptor mbVEGFR2 sits at the crossroads of VA/LA initiation. Our proposed research strategy will define the role mbVEGFR2 plays in maintaining the vascular/avascular balance at the corneal border in both the normal and injured eye, increase our understanding of the VEGFR2-R3 relationship, and separate the relative contributions of pro-angiogenic agents and mbVEGFR2 to proliferation, migration, and tube formation. A better understanding of the role this receptor plays in both the normal and injured eye is of clinical importance because it increases our ability to develop therapeutic methods to prevent or reverse pathological VA and LA in the cornea, in other transplant procedures, and in tumor growth and metastasis.

描述（由申请人提供）：角膜新血管形成（NV）是一种常见的，残疾的状况，是可能遵循角膜损伤或感染的主要原因。我们的长期目标是表征VEGF受体在两个中央角膜血管化过程中的作用，血管血管生成（VA）和淋巴管生成（LA）。 LA中VEGFR-2（SVEGFR-2）上皮，可溶性形式的参与已得到很好的特征。然而，膜结合，血管VEGFR-2（MBVEGFR-2）在角膜VA和LA中的作用尚未。这些提出的实验旨在表征VEGFR-2膜结合的同工型的潜在血管生成和淋巴管生成作用。我们提出了这样一个假设，即血管MBVEGFR2可能在角膜血管生成/淋巴管生成中的VEGF-A（to va）或VEGF-C（to va）或VEGF-C（to vegf-a（to va）或VEGF-C（to La）的诱导响应。已经提出了两个具体目的来表征VEGFR-2在角膜血管生成和淋巴管生成中的作用。 AIM A.使用诱导的条件敲除小鼠线来确定MBVEGFR2是否保持与角膜中SVEGFR1和SVEGFR2的平衡关系。 AIM B.表征促血管生成剂在VEGFR活性以及VA/LA的启动，进展和维持方面的各个作用。意义：内皮受体MBVEGFR2位于VA/LA启动的十字路口。我们提出的研究策略将定义MBVEGFR2在正常和受伤的眼睛中维持角膜边界处的血管/血管平衡的作用，增强我们对VEGFR2-R3关系的理解，并分离亲抗毒剂的相对贡献，以及MBVEGGFR2对增殖，移民和管形成的相对贡献。更好地理解该受体在正常眼和受伤的眼睛中的作用是临床重要性，因为它增加了我们开发治疗方法，以预防或逆转病理VA和LA在角膜中，其他移植程序以及肿瘤生长和转移的能力。