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 识别易患这些疾病的基因的方法， 尤其是非洲人后裔。特点待 在培养细胞中研究的是那些被报道异常调节的细胞 在纤维增生性疾病中，即疤痕疙瘩和类风湿病 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 纤连蛋白。要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 佛波酯。要检验的一般假设是： (I) 缺陷 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征 纤维化病变，例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SMC、子宫纤维瘤SMC； (2) 特定基因的突变易导致纤维增生 非洲人后裔的疾病。 具体目标是： 1. 确定纤维化病变细胞是否与正常细胞不同 细胞通过上述调节生长和基质合成 效应器； 2. 通过确定这些差异的机制来表征 参与失调的信号转导途径的步骤 以及基因表达途径中发生错误调节的步骤 发生； 3. 使用位置克隆技术来鉴定负责的基因 疤痕疙瘩和高血压。