GROWTH FACTOR EFFECTS ON PROXIMAL TUBULE TRANSPORT

生长因子对近端肾小管运输的影响

• 批准号: 3081132
• 负责人: RAYMOND P QUIGLEY
• 金额: $ 7.56万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3081132
• 关键词: antireceptor antibody; biological fluid transport; epidermal growth factor; growth factor receptors; kidney function; laboratory rabbit; monoclonal antibody; perfusion; protein kinase C; receptor binding; receptor coupling; receptor expression; renal tubule; second messengers; tissue /cell culture; transforming growth factors; western blottings

Peptide growth factors play important roles in renal function, disease response and development. In particular, EGF has many effects in the kidney. We have recently shown that EGF has a specific effect on PCT transport to stimulate phosphate transport (Quigley, R and M. Baum, 1991, Epidermal growth factor (EGF) stimulates phosphate transport (J-phos) in the rabbit proximal convoluted tubule (PCT), J. Am. Soc,. Nephrol. 2:444A). TGFalpha binds to the EGF receptor to elicit its effects and should therefore have similar effects to EGF. In the PCT, however, TGFalpha stimulated phosphate transport at a concentration that was one-hundredth that of EGF. In addition, TGFalpha also stimulated volume absorption, glucose transport and bicarbonate transport. The current proposal is designed to examine these differential effects of EGF and TGFalpha in the PCT. The aims of this proposal are: 1) further define the differences in the effects of EGF and TGFalpha on PCT solute transport, 2) examine the binding of EGF and TGFalpha to the PCT to determine if there are separate binding sites, 3) examine the second messenger systems employed by EGF and TGFalpha in intracellular signalling in the PCT, and 4) determine the metabolic processing of the ligand-receptor complex of EGF and TGFalpha in renal tissue. The techniques employed in this proposal include in vitro microperfusion of PCT, binding studies, primary cell culture, immunoblots of phosphotyrosine proteins, measurements of Ip3, DAG and intracellular calcium, and pulse-chase experiments.

肽生长因子在肾功能中起重要作用， 疾病反应和发育。 特别是，EGF有很多 肾脏的影响。 我们最近表明EGF有一个 对PCT转运的特定影响以刺激磷酸盐转运 （Quigley，R和M. Baum，1991年，表皮生长因子（EGF） 刺激兔近端的磷酸转运（J-Phos） 休息小管（PCT），J。Am。 Soc，。 肾脏。 2：444a）。 tgfalpha 与EGF受体结合以引起其作用，因此应 与EGF具有相似的影响。 但是，在PCT中，TGFALPHA 以浓度为浓度的磷酸盐转运 EGF的一百分之一。 另外，TGFALPHA也刺激了 体积吸收，葡萄糖转运和碳酸氢盐转运。 这 当前的建议旨在检查这些差异效果 PCT中的EGF和TGFALPHA。 该提议的目的是：1）进一步定义 EGF和TGFALPHA对PCT溶质传输的影响，2）检查 EGF和TGFALPHA与PCT的结合，以确定是否存在 单独的绑定站点，3）检查第二使者系统 EGF和TGFALPHA在PCT中的细胞内信号传导中使用 4）确定配体受体的代谢加工 EGF和TGFALPHA在肾组织中的复合物。 技术 该提案中使用的是PCT的体外微灌注 结合研究，原代细胞培养，免疫印迹 磷酸酪氨酸蛋白，IP3，DAG和细胞内的测量值 钙和脉搏追踪实验。