PKC Signaling in Thrombin-Activated Lung Fibroblasts

凝血酶激活的肺成纤维细胞中的 PKC 信号转导

• 批准号: 6622381
• 负责人: GALINA S BOGATKEVICH
• 金额: $ 5.63万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6622381
• 关键词: G protein coupled receptor kinase; affinity chromatography; autoimmune disorder; binding proteins; biological signal transduction; confocal scanning microscopy; connective tissue disorder; cytoskeleton; enzyme activity; fibroblasts; fibrosis; histones; immunoprecipitation; lung; pathologic process; phenotype; phosphorylation; postdoctoral investigator; protein kinase C; protein localization; protein purification; protein transport; pulmonary fibrosis /granuloma; systemic scleroderma; thrombin; tissue /cell culture

DESCRIPTION (provided by applicant):Scleroderma (systemic sclerosis, SSc) is an autoimmune, connective tissue disease characterized by microvascular injury and fibrosis, affecting 250,000 people (mostly women) in the USA. A leading cause of death in scleroderma patients is pulmonary dysfunction as a result of progressive interstitial lung fibrosis. It is postulated that activated fibroblasts (myofibroblasts) are involved in the pathogenesis of lung fibrosis. One mediator of lung fibroblast activation is thrombin, a multifunctional serine protease and G-protein coupled receptor ligand, which is generated immediately at sites of vascular injury. Recently we observed that exposure of normal cultured human lung fibroblasts to thrombin induces the myofibroblast phenotype. This change to an SSc phenotype occurs via protein kinase C epsilon (PKC-e) signal transduction. These observations open an interesting avenue in the investigation of the pathogenesis of SSc. Our overlying hypothesis is that thrombin triggers distinct PKC signaling mechanisms in normal and SSc lung fibroblasts. Specificity of the responses mediated in these two cell types can be explained by interaction of PKC with specific anchoring proteins. Better understanding of the mechanisms of these interactions may provide a useful target for novel therapeutic interventions in scleroderma lung disease, for which no proven, effective therapy exists.

描述（由申请人提供）：硬皮病（系统性硬化症，SSc）是一种疾病