Syndecan-2 and Clinical Progression of Idiopathic Pulmonary Fibrosis

Syndecan-2 与特发性肺纤维化的临床进展

• 批准号: 8018538
• 负责人: Ivan O. Rosas
• 金额: $ 15.19万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-04 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8018538
• 关键词: Acute; Acute Disease; Address; Affect; Alveolar; Alveolar Macrophages; Binding; Biological Assay; Biological Availability; Blood; CCL2 gene; Candidate Disease Gene; Cause of Death; Cells; Clinical; Co-Immunoprecipitations; Cohort Studies; Collaborations; Critical Care; Development; Disease; Disease Progression; Endothelial Cells; Extracellular Matrix Proteins; Family; Fibroblast Growth Factor; Fibrosis; Fostering; Foundations; Future; Gel; Gene Expression; Gene Expression Profiling; Genes; Goals; Growth Factor; HL60; Hamman-Rich syndrome; Heparan Sulfate Proteoglycan; Hospitalization; Human; Hypersensitivity; Individual; Injury; Interstitial Collagenase; Interstitial Lung Diseases; Irrigation; Knowledge; Laboratories; Length of Stay; Leukocytes; Ligands; Lung; Lung Lavage Fluid; Lung diseases; Matrix Metalloproteinases; Measurement; Medical; Medicine; Membrane; Microarray Analysis; Multi-Institutional Clinical Trial; Pathogenesis; Patients; Pattern; Peptide Hydrolases; Proteins; Proteomics; Receptor Signaling; Regulation; Research; Research Personnel; Respiration Disorders; Role; Severities; Severity of illness; Signal Transduction; Stable Disease; Staging; Structure of parenchyma of lung; Testing; Therapeutic; Transforming Growth Factor beta; United States; United States National Institutes of Health; Universities; Up-Regulation; base; career; chemokine; chemokine receptor; cohort; cytokine; eosinophil; experience; fibroglycan; insight; macrophage; member; neutrophil; outcome forecast; overexpression; peripheral blood; programs; protein protein interaction; receptor binding; research study; skills; syndecan

The purpose of this proposal is to foster the scientific development and laboratory skills of Dr. Ivan Rosas in order that the candidate may become an independent investigator. The Pulmonary, Allergy and Critical Care Medicine Division at the University of Pittsburgh and it's Simmons Interstitial Lung Disease Center will provide the candidate with the ideal setting in which to test the hypothesis that clinical disease progression in IPF patients is associated with increases in Syndecan-2 expression and shedding. In order to identify candidate genes involved in the progression of IPF, the candidate performed microarray and targeted proteomic analysis of alveolar macrophages, broncho-alveolar lavage (BAL) and peripheral blood of IPF patients. He analyzed gene expression patterns in alveolar macrophages, and found that Syndecan-2 was upregulated. More importantly, the upregulation of Syndecan-2 correlated with disease severity in the study cohort. Syndecan-2, a member of the syndecan family of heparan-sulfate proteoglycans, can bind multiple chemokines, cytokines, growth factors and extracellular matrix proteins. Syndecan-2 can bind to these molecules as a membrane bound or shed protein. Although little is known about shedding and regulation of syndecans in human lung disease, they are known targets for matrix metallo-proteases (MMP's), which are highly abundant in the lungs of patients with IPF. The specific aims of this proposal are: 1 To determine whether SDC2 levels are indicative and predictive of disease development and progression. 2.To determine what MMP's, increased in IPF, regulate Syndecan-2 shedding. 3.To determine the effects of syndecan expression and shedding on chemokine and growth factor bioavailability. The proposed research will offer insight into the role of Syndecan-2 in IPF disease progression. The knowledge obtained during the period of support will be the foundation for future studies determining the therapeutic potential of modulating levels of MMP's and heparan-sulfate proteoglycans in patients with IPF. Through the collaboration with Dr. Kaminski, Dr. Choi and a network of experienced researchers, the candidate will obtain the foundation for the development of an independent academic career.

该提议的目的是促进伊万·罗萨斯博士的科学发展和实验室技能 命令候选人可以成为独立的调查员。肺，过敏和重症监护 匹兹堡大学的医学系及其西蒙斯间质肺病中心将 为候选人提供一个理想的环境，以检验临床疾病进展的假设 IPF患者与Syndecan-2表达和脱落的增加有关。 为了识别IPF进展涉及的候选基因，候选人进行了微阵列 牙槽巨噬细胞，支气管 - 肺泡灌洗（BAL）和周围的靶向蛋白质组学分析 IPF患者的血液。他分析了肺泡巨噬细胞中的基因表达模式，并发现 Syndecan-2上调。更重要的是，Syndecan-2的上调与疾病相关 研究队列中的严重程度。 Syndecan-2，Syndecan家族的乙酰硫酸盐家族的成员 蛋白聚糖可以结合多种趋化因子，细胞因子，生长因子和细胞外基质蛋白。 Syndecan-2可以与这些分子结合，作为膜结合或脱落蛋白。虽然鲜为人知 关于人类肺部疾病中联合体的脱落和调节，它们是矩阵的靶标 金属蛋白酶（MMP），在IPF患者的肺中高度丰富。 该提案的具体目的是：1确定SDC2水平是否指示和预测 疾病发展和进展。 2.确定IPF增加的MMP调节Syndecan-2 脱落。 3.确定联合表达和脱落对趋化因子和生长因子的影响 生物利用度。拟议的研究将洞悉Syndecan-2在IPF疾病中的作用 进展。在支持期间获得的知识将是未来研究的基础 确定调节MMP水平和乙酰硫酸乙酯蛋白聚糖的治疗潜力 IPF患者。通过与Kaminski博士，Choi博士和经验丰富的网络的合作 研究人员，候选人将获得开发独立学术的基础 职业。