KELOIDS--AN IN VITRO MODEL OF FIBROPROLIFERATIVE DISEASE

瘢痕疙瘩——纤维增生性疾病的体外模型

• 批准号: 6107047
• 负责人: Shirley B. Russell
• 金额: $ 7.35万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107047
• 关键词: biological models; cell growth regulation; collagen; disease /disorder proneness /risk; elastin; extracellular matrix proteins; fibroblasts; fibronectins; gene expression; gene mutation; human tissue; interleukin 1; keloid skin disorder; molecular cloning; neoplastic growth; phorbols; prostaglandins; protein biosynthesis; radioimmunoassay; radionuclides; regulatory gene; smooth muscle; tissue /cell culture; transcription factor; transforming growth factors

The long term goal of this multidisciplinary project is to identify abnormal regulatory characteristics of fibroblasts and smooth muscle cells (SMC) cultured from fibrotic lesions in order to elucidate the pathogenesis of fibroproliferative disorders, and to use genetic approaches to identify genes that predispose to these conditions, particularly in persons of African descent. Characteristics to be studied in cultured cells are those reported to be abnormally regulated in fibroproliferative conditions, i.e., keloids and rheumatoid arthritis. Responses to be examined are cell growth and synthesis of matrix proteins, specifically, collagen, elastin, and fibronectin. Effectors to be studied include hydrocortisone, transforming growth factor beta, interleukin-1, prostaglandins and phorbol esters. General hypotheses to be tested are: (I) a defect in a regulatory mechanism that controls growth and matrix synthesis accounts for the fibroproliferative characteristics of cells from fibrotic lesions, e.g., keloid fibroblasts, gingival fibroblasts from chronic periodontitis, atherosclerotic SMC, and uterine fibroma SMC; and (2) mutations in specific genes predispose to fibroproliferative disorders in persons of African descent. Specific aims are: 1. determine whether cells from fibrotic lesions differ from normal cells in regulation of growth and matrix synthesis by the above effectors; 2. characterize the mechanisms of these differences by determining the step(s) on the signal transduction pathway involved in misregulation and the step on the gene expression pathway at which misregulation occurs; 3. use position cloning techniques to identify genes responsible for keloids and hypertension.

这个多学科项目的长期目标是确定 成纤维细胞和平滑肌的异常调节特性 从纤维化病变中培养的细胞(SMC)，以阐明 纤维增生性疾病的发病机制，并利用遗传学 识别易患这些疾病的基因的方法， 特别是在非洲人后裔中。应具备的特点 在培养细胞中研究的是据报道被异常调节的那些 在纤维增生性条件下，即瘢痕疙瘩和类风湿 关节炎。要检查的反应是细胞生长和合成 基质蛋白，特别是胶原蛋白、弹性蛋白和 纤维连接蛋白。待研究的效应物包括氢化可的松， 转化生长因子β、白介素1、前列腺素和 佛波醇酯。需要检验的一般假设是：(I) 控制生长和基质合成的调节机制 解释了细胞的纤维增殖特性 纤维性病变，如瘢痕疙瘩成纤维细胞，牙龈成纤维细胞 慢性牙周炎、动脉粥样硬化性SMC和子宫纤维瘤SMC； 以及(2)特定基因突变易导致纤维增生性疾病 非洲人后裔的精神障碍。 具体目标是： 1.确定纤维化病变的细胞是否与正常细胞不同。 上述物质对细胞生长和基质合成的调节作用 效应器； 2.通过确定 S步入调控失调的信号转导通路 以及基因表达途径上的一步，即错误调节 发生； 3.使用位置克隆技术识别负责 瘢痕疙瘩和高血压。