RPG: Proteoglycans: Secondary Regulators of Growth Factor Activity

RPG：蛋白聚糖：生长因子活性的二级调节剂

• 批准号: 9629100
• 负责人: Kimberly Williams
• 金额: $ 1.8万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-15 至 1997-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9629100&HistoricalAwards=false
• 关键词: RPG; Proteoglycans; Secondary; Regulators; Growth

9629100 Forsten This is a Research Planning Grant for Women Scientists and Engineers. The overall objective of this research is to understand how the local cellular environment influences accessibility of growth factors to target stimulatory cells. IGF-I, an endocrine factor, is found almost exclusively in serum bound to a subset of a family of specific binding proteins known as the insulin-like growth factor binding proteins (IGFBP). Endothelial secreted proteoglycans may impact IGF-I activity through regulation of IGFBP binding. The hypothesis of this proposal is that vascular endothelial cells secrete heparan sulfate proteoglycans (P-HS) which can displace and thereby liberate IGF-I from serum binding proteins (IGFBP-3). This liberation will affect IGF-I binding to receptors on endothelial cells, and consequently transport of IGF-I by endothelial cells to the underlying tissue. Presently, it is not clear whether P-HS will potentiate or inhibit accessibility. The specific aims of the overall research project are to: 1, determine if P-HS influences IGF-I binding to bovine aortic endothelial cells (BAE) in the absence or presence of IGFBP; 2, evaluate how cell density and IGF-I addition impact P-HS secretion by BAE; 3, measure the effect of P-HS on IGFBP-3, IGF-I, and IGFBP-3/IGF-I complex (cell-free); and develop and validate a mathematical model incorporating all the elements of the IGF-I/BAE system. In order to plan for the full research proposal, the following activities will be done during the research planning period: 1, obtain and purify P-HS from endothelial conditioned medium; 2, demonstrate an effect of P-HS addition on IGF-I binding to BAE; 3, determine if P-HS binds to IGF-I/IGFBP-3 and if IGF-I can be liberated from the complex; and 4, develop a quantitative binding assay for P-HS binding to the complex and determine if the effect is proteoglycan specific. ***

9629100 Forsten这是一项针对女性科学家和工程师的研究计划资助。本研究的总体目标是了解局部细胞环境如何影响生长因子对目标刺激细胞的可及性。igf - 1是一种内分泌因子，几乎只存在于血清中，与胰岛素样生长因子结合蛋白（IGFBP）家族的一个亚群结合。内皮分泌的蛋白聚糖可能通过调节IGFBP结合影响IGF-I活性。该假说认为血管内皮细胞分泌硫酸肝素蛋白聚糖（P-HS），可取代血清结合蛋白（IGFBP-3），从而释放igf - 1。这种释放会影响igf - 1与内皮细胞上受体的结合，从而影响igf - 1由内皮细胞转运到下层组织。目前尚不清楚P-HS是否会增强或抑制可及性。整个研究项目的具体目标是：1，确定在没有或存在IGFBP的情况下，P-HS是否影响IGF-I与牛主动脉内皮细胞（BAE）的结合；2、评价细胞密度和添加IGF-I对BAE分泌P-HS的影响；3、测定P-HS对IGFBP-3、IGF-I和IGFBP-3/IGF-I复合物（无细胞）的影响；并开发和验证包含IGF-I/BAE系统所有元素的数学模型。为了规划完整的研究计划，在研究计划期间将进行以下活动：1，从内皮条件培养基中获得并纯化P-HS；2、证明添加P-HS对IGF-I与BAE结合的影响；3、确定P-HS是否与IGF-I/IGFBP-3结合，以及IGF-I是否能从复合物中释放出来；4、开发P-HS与复合物结合的定量结合试验，并确定其效果是否具有蛋白多糖特异性。＊＊＊