FGF SIGNAL TRANSDUCTION IN VASCULAR CELLS

描述（改编自研究者摘要）：血管内皮 细胞增殖与许多疾病的发病机制有关， 血管生成疾病（例如，癌症、糖尿病视网膜病变），而平滑肌 细胞积累发生在动脉粥样硬化的发展过程中， 移植相关动脉硬化和血管壁后再狭窄 损伤 成纤维细胞生长因子（FGF）可能在 在EC和SMC生长控制中起重要作用。 在目前的融资过程中 在此期间，申请人启动了一项新的研究计划，以确定和 表征FGF诱导基因。 差异显示策略是 成功地用于获得代表13个FGF-1应答的cDNA克隆 在鼠NIH 3 T3成纤维细胞中表达的基因。 在本申请中， 提出实验来详细表征这些基因之一。 这 预测Fn 14基因编码一种新的14 kDa的完整质膜 蛋白 根据初步数据，申请人假设Fn 14 参与生长因子信号传导和细胞周期进程。 的 具体目的是：1）确定Fn 14蛋白是否在 在促分裂原刺激的细胞中水平升高，并表征Fn 14 使用抗Fn 14在小鼠胚胎和组织中的细胞分布 抗体的 2)为了确定Fn 14是否是秘书， 膜相关蛋白或胞质蛋白 实验方法。 3)为了确定Fn 14是否起重要作用， 通过分析细胞的生长特性， 表达Fn 14蛋白水平升高或降低的细胞。 是 预计这些研究将提供新的信息 生长因子信号转导的机制，也可能确定一个新的 血管细胞抗增殖治疗的治疗靶点。

DESCRIPTION (Adapted from Investigator's Abstract): Vascular endothelial cell proliferation is associated with the pathogenesis of numerous angiogenic diseases (e.g., cancer, diabetic retinopathy) while smooth muscle cell accumulation occurs during the development of atherosclerosis, transplant associated arteriosclerosis and restenosis after vessel wall injury. It is likely that the fibroblast growth factors (FGF) play an important role in EC and SMC growth control. During the present funding period, the applicant initiated a new research program to identify and characterize FGF-inducible genes. A differential display strategy was successfully used to obtain cDNA clones representing 13 FGF-1 responsive genes expressed in murine NIH 3T3 fibroblasts. In this application, experiments are proposed to characterize in detail one of these genes. This gene (Fn14) is predicted to encode a novel, 14 kDa integral plasma membrane protein. Based upon preliminary data the applicant hypothesizes that Fn14 is involved in growth factor signaling and cell cycle progression. The Specific Aims are: 1) To determine whether the Fn14 protein is expressed at elevated levels in mitogen-stimulated cells and to characterize Fn14 cellular distribution in mouse embryos and tissues using anti-Fn14 antibodies. 2) To determine whether Fn14 is a secretary, membrane-associated or cytosolic protein using several alternative experimental approaches. 3) To determine whether Fn14 plays an important role in cellular proliferation by analyzing the growth properties of cells that express either elevated or reduced levels of the Fn14 protein. It is anticipated that these studies will provide novel information on the mechanism of growth factor signal transduction and may also identify a new therapeutic target for vascular cell antiproliferative therapy.