Endostatin-derived Short Peptides in Corneal Transplantation

内皮抑素衍生的短肽在角膜移植中的应用

• 批准号: 9280824
• 负责人: JIN-HONG CHANG
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9280824
• 关键词: Affect; Affinity; Alanine; Animal Model; Binding; Biological Assay; Biological Models; Blindness; Blood; Blood Vessels; CD8B1 gene; Cell Proliferation; Cells; Clinical; Collagen; Collagen Type XVIII; Cornea; Corneal Injury; Corneal Neovascularization; Corneal Stroma; Disease; Endostatins; Endothelial Cells; Environment; Epithelial; Exhibits; Explosion; Exposure to; Eye Injuries; Future; Graft Rejection; Growth; Health; Healthcare; Human Resources; Immunoprecipitation; In Vitro; Incidence; Infection; Injury; Invaded; KDR gene; Keratoplasty; Knock-out; Knockout Mice; Ligands; Lymphangiogenesis; Lymphatic Endothelial Cells; Lymphatic vessel; Mediating; Mediator of activation protein; Membrane; Messenger RNA; Methods; Mission; Modeling; Molecular; Mus; Mustard Gas; Operative Surgical Procedures; Pathologic; Penetration; Peptides; Physiological; Prevalence; Production; Proteins; Receptor Protein-Tyrosine Kinases; Recovery; Research; Role; Scanning; Specificity; Surface Plasmon Resonance; Testing; Tissue Donors; Tissue Transplantation; Tissues; Transplantation; Trauma; United States; Ursidae Family; VEGF Trap; VEGFA gene; Vascular Endothelial Cell; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-3; Vascular Endothelial Growth Factors; Vascularization; Veterans; Work; angiogenesis; cell motility; combat; common treatment; corneal epithelium; drug development; effective therapy; experience; experimental study; high risk; improved; macrophage; neovascularization; new growth; novel therapeutics; pressure; prevent; public health relevance; receptor; receptor binding; response; success

DESCRIPTION (provided by applicant): Endostatin-derived short peptide in corneal transplantation Abstract: Ocular trauma's ranking as the fourth most common injury among combat personnel indicates the vital importance of evaluating and promoting ocular health among veterans. Corneal neovascularization, or the growth of new blood vessels (angiogenesis) and new lymphatic vessels (lymphangiogenesis) in the cornea, often results from infection or severe corneal injury including explosion pressure, penetration by debris, or long-term exposure to dry environments. Preventing corneal neovascularization generally necessitates in high risk corneal transplantation in order to restore eyesight and prevent blindness. Approximately 40,000 corneal transplants are performed in the United States annually, but new blood vessel growth in either the original or transplanted cornea significantly diminishes treatment success rates. For example, the rate of rejected corneas that are introduced into avascular hosts is 0-10%, compared to the significantly increased rate of 25-50% among hosts that are severely vascularized. The discovery of specific lymphatic vessel markers has improved our understanding of lymphangiogenesis. However, no effective treatment to prevent corneal vessel growth after corneal transplantation currently exists. Collagen XVIII (col18a1) and its cleavage products (endostatin, neostatin-7 and endostatin-derived peptides) have been identified as modulators of corneal angiogenesis and lymphangiogenesis and therefore of corneal transplant rejection. Endostatin competes with pro-angiogenic Vascular Endothelial Growth Factors (VEGFs) for binding to the tyrosine-kinase receptors, VEGFRs, that are necessary to mediate the effects of VEGFs. VEGFR-1 and -2 are two receptors that are primary mediators of angiogenesis and lymphangiogenesis in the corneal stroma and epithelium. In our experiment, we propose to use high-risk mouse corneal transplantation models with collagen XVIII knockout, Lecre-VEGFR1lox and lecre-VEGFR2lox mouse as recipients with endostatin-derived short peptide and VEGF traps, to determine the most effective strategies for inhibiting corneal blood and lymphatic vessel growth. In so doing, we hope to identify components that effectively modulate corneal neovascularization in order to facilitate the future development of drugs that will improve corneal transplant success rates. Our research will bear implications that are not only pertinent to the Veteran Affairs healthcare mission, promoting ocular health and preventing blindness among veterans, but also indicate methods for successful transplantation of tissues other than just the cornea.

描述（由申请人提供）： 角膜移植中的内接抑制素的短肽摘要：眼部创伤是战斗人员中第四个最常见的伤害，这表明评估和促进退伍军人的眼部健康的重要性至关重要。角膜新血管或新血管（血管生成）和角膜中新的淋巴管（淋巴管生成）的生长通常是由感染或严重的角膜损伤引起的，包括爆炸压力，碎屑渗透或长期暴露于干燥环境中。防止角膜新血管形成通常需要进行高风险的角膜移植，以恢复视力并防止失明。每年在美国进行大约40,000次角膜移植，但原始或移植的角膜的新血管生长显着降低了治疗的成功率。例如，被引入血管宿主的拒绝角膜速率为0-10％，而严重血管化的宿主中的25-50％的速率显着提高。特异性淋巴血管标记的发现增强了我们对淋巴管生成的理解。但是，目前存在角膜移植后无法防止角膜血管生长的有效治疗。胶原蛋白XVIII（COL18A1）及其裂解产物（内抑素，Neostatin-7和内抑素衍生的肽）已被鉴定为角膜血管生成和淋巴管生成的调节剂，因此是角膜移植剂的抑制作用。内抑素与亲血管生成的血管内皮生长因子（VEGF）竞争，以与酪氨酸激酶受体VEGFRS结合，这是介导VEGFS的影响所必需的。 VEGFR -1和-2是两个受体，它们是角膜基质和上皮中血管生成和淋巴管生成的主要介体。在我们的实验中，我们建议使用胶原蛋白XVIII敲除，Lecre-VEGFR1LOX和Lecre-VEGFR2LOX小鼠使用高风险的小鼠角膜移植模型作为具有内接源性短肽和VEGF陷阱的受体，以确定抑制毛孔血液和Lymphatate果皮生长的最有效策略。这样一来，我们希望确定有效调节角膜新血管形成的组件，以促进未来的药物发展，以提高角膜移植成功率。我们的研究将具有与退伍军人事务医疗任务相关的意义，促进眼部健康和预防退伍军人的失明，而且还指出了成功移植其他组织以外的方法的方法。

项目成果

Tetra-aqua-tetra-kis-(4,4'-bipyridine dioxide-κO)terbium(III) octa-cyanidotungstate(V).

四-水-四-kis-(4,4-二氧化联吡啶-γO)铽(III)八氰钨酸盐(V)。

• DOI: 10.1107/s1600536812005004
• 发表时间: 2012
• 期刊: Acta crystallographica. Section E, Structure reports online
• 作者: Shi,Yu-Sheng;Ran,Mao-Qian;Chen,Ying-Ying;Yuan,Ai-Hua
• 通讯作者: Yuan,Ai-Hua

Quantification of Angiogenesis and Lymphangiogenesis in the Dual ex vivo Aortic and Thoracic Duct Assay.

双离体主动脉和胸导管测定中血管生成和淋巴管生成的定量。

• DOI: 10.2174/0929866526666190925145842
• 发表时间: 2020
• 期刊: Protein and peptide letters
• 影响因子: 1.6
• 作者: Wang,Shuangyong;Yamakawa,Michael;Santosa,SamuelM;Chawla,Neeraj;Guo,Kai;Montana,Mario;Hallak,JoelleA;Han,Kyu-Yeon;Ema,Masatsugu;Rosenblatt,MarkI;Chang,Jin-Hong;Azar,DimitriT
• 通讯作者: Azar,DimitriT