Regulation of Basic Fibroblast Growth Factor Gene Expressionin Reactive and Neoplastic Astrocytes

反应性星形胶质细胞和肿瘤性星形胶质细胞中碱性成纤维细胞生长因子基因表达的调节

• 批准号: 9411226
• 负责人: Michal Stachowiak
• 金额: $ 27.8万
• 依托单位: Barrow Neurological Institute
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9411226&HistoricalAwards=false
• 关键词: Regulation; Basic; Fibroblast; Growth; Factor

The two major cell types that form the nervous system are neurons and glial cells. Genesis of glial and neuronal cells, their differentiation and maturation in developing nervous system are thought to be controlled by proteins (growth factors) expressed at individual developmental stages. Controlled expression of growth factors may also underlie the plasticity that occurs in the adult nervous system during learning or regeneration of nervous tissue (stimulation of cells). Aberrant expression of growth factors has been implicated in the transformation of normal glial cells to tumorigenic glioma cells. Hence, to understand development, adult plasticity of the nervous tissue, and tumorigenic transformation it is essential to elucidate mechanisms that control expression of genes encoding growth factor proteins. One such protein is basic fibroblast growth factor (bFGF). Elucidation of the mechanisms controlling expression of the gene that encodes the bFGF protein is of the highest priority. Very little is known about regulation of this protein which is critical for neural and glial development and plasticity. The PI's have revealed that expression of the BFGF gene is transiently increased during reversible transition of quiescent (nondividing) glial cells to reactive (actively dividing) glia. Such reversible activation of glia is thought to play a role in neural development and in the support of adult neural plasticity. The PI has also shown that expression of the bFGF gene is permanently increased in irreversibly transformed tumorigenic glioma cells. In both cases increased expression of bFGF gene was responsible for the changes in the biology of glia (transient and permanent induction of cell proliferation). The overall aim of this project is to determine the molecular mechanisms underlying the above-mentioned changes in bFGF gene expression. The analysis of the bFGF gene has indicated that there are fundamental differences in the mechanisms by which t his gene is regulated as compared to other genes, and that novel mechanisms are involved in the regulation of bFGF gene. Identification of those mechanisms will lead to a better understanding of the molecular events controlling the biology of glial cells in the developing and adult nervous system.

构成神经系统的两种主要细胞类型是神经元细胞和神经胶质细胞。神经系统中胶质细胞和神经元细胞的发生、分化和成熟被认为是由个体发育阶段表达的蛋白质（生长因子）控制的。生长因子的受控表达也可能是成人神经系统在学习或神经组织再生（刺激细胞）过程中可塑性的基础。生长因子的异常表达与正常胶质细胞向致瘤性胶质瘤细胞的转化有关。因此，为了了解神经组织的发育、成体可塑性和致瘤性转化，有必要阐明控制编码生长因子蛋白的基因表达的机制。其中一种蛋白质是碱性成纤维细胞生长因子（bFGF）。调控bFGF蛋白编码基因表达的机制的阐明是当务之急。对于这种对神经和胶质发育和可塑性至关重要的蛋白质的调控，我们所知甚少。PI显示，在静止（非分裂）胶质细胞向反应（积极分裂）胶质细胞可逆转变期间，BFGF基因的表达短暂增加。这种可逆的胶质细胞激活被认为在神经发育和支持成人神经可塑性中发挥作用。PI还显示bFGF基因的表达在不可逆转化的致瘤性胶质瘤细胞中永久增加。在这两种情况下，bFGF基因的表达增加都是胶质细胞生物学变化的原因（短暂和永久诱导细胞增殖）。该项目的总体目标是确定上述bFGF基因表达变化的分子机制。对bFGF基因的分析表明，与其他基因相比，bFGF基因的调控机制存在着根本的差异，并且存在着新的调控机制。这些机制的识别将有助于更好地理解发育和成人神经系统中控制胶质细胞生物学的分子事件。