KELOIDS--AN IN VITRO MODEL OF FIBROPROLIFERATIVE DISEASE

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 细胞（SMC）培养的纤维化病变，以阐明 纤维增生性疾病的发病机制，并使用遗传 鉴定易患这些疾病的基因的方法， 特别是非洲人后裔。特性的 在培养细胞中研究的是那些被报道为异常调节的细胞， 在纤维增生性病症中，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 纤连蛋白。待研究的效应物包括氢化可的松， 转化生长因子β、白细胞介素-1、胰高血糖素和 佛波醇酯需要检验的一般假设是：（一） 控制生长和基质合成的调节机制 解释了来自于细胞的纤维增生特征， 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和子宫纤维瘤SMC; 和（2）特定基因的突变使纤维增生易感 非洲人后裔的疾病。 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 通过上述方式调节细胞的生长和基质合成 效应器; 2.通过确定这些差异的机制， 参与误调节的信号转导途径上的步骤 以及基因表达途径中的一步， 发生; 3.使用定位克隆技术来鉴定负责 瘢痕疙瘩和高血压。

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.