COMPENSATORY HYPERTROPHY OF THE KIDNEY

肾脏代偿性肥大

• 批准号: 3232431
• 负责人: LEON G FINE
• 金额: $ 17.03万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232431
• 关键词: amiloride; antiport; apical membrane; disease /disorder model; hormone regulation /control mechanism; insulin; kidney cell; kidney hypertrophy; laboratory rabbit; membrane potentials; mitogens; prostaglandin E; receptor; sodium chloride

The purpose of the proposed studies is to establish an in vitro model of renal tubular hypertrophy and to examine whether a unifying mechanism can be found for the initiation of cell hypertrophy. Prior studies have suggested that a flow-induced increase in luminal Na-H antiport occurs in the proximal tubules of kidneys with reduced nephron populations and it is possible that this signal (either Na influx or intracellular alkalization) initiates the process of cell growth. Many mitogens stimulate cell proliferation by inducing an early increase in Na-H antiport. A primary culture of proximal tubular cells grown in serum-free hormone supplemented medium will be stimulated to hypertrophy by prolonged exposure to insulin, prostaglandin E1 and hypertonic sodium chloride. The existence of a luminal Na-H antiporter will be demonstrated by measuring Na influx kinetics and H+ efflux rates in intact cells. We will study the acute effects of the hypertrophic stimuli on these transport processes and the respective stimulatory and inhibitory effects of a transmembrane H+ gradient and amiloride, a competitive inhibitor, of the Na-H antiport. The steady-state rate of Na-H antiport will be studied in hypertrophied vs. non-hypertrophied cells and the ability of prolonged exposure to amiloride to inhibit the hypertrophic response will be evaluated. Our ability to induce hypertrophy without cell proliferation in this experimental model using a variety of completely different stimuli (i.e., hormonal and ionic) will make it possible to ascertain whether a single initiating event is common to the process of cell growth. If increased Na-H antiport is consistently found, it is likely that this could be the event which initiates hypertrophy of renal tubular cells in vivo.

拟议研究的目的是建立一个体外模型 肾小管肥大并检查统一机制是否可以 发现细胞肥大的起始。 先前的研究有 表明流引起的管腔 Na-H 反向端口增加发生在 肾近端小管肾单位数量减少， 可能是这个信号（Na 流入或细胞内碱化） 启动细胞生长过程。 许多有丝分裂原刺激细胞 通过诱导 Na-H 反向转运的早期增加来增殖。 初级 添加无血清激素的近端肾小管细胞培养物 长时间暴露于胰岛素会刺激培养基肥大， 前列腺素E1和高渗氯化钠。 存在一个 管腔 Na-H 逆向转运蛋白将通过测量 Na 流入来证明 完整细胞中的动力学和 H+ 流出率。 我们将研究急性 肥大刺激对这些运输过程的影响以及 跨膜H+各自的刺激和抑制作用 Na-H 反向转运的梯度和阿米洛利（一种竞争性抑制剂）。 这 将在肥大与肥大中研究 Na-H 反向转运的稳态速率。 非肥大细胞和长期暴露于阿米洛利的能力 将评估抑制肥大反应的效果。 我们的能力 在此实验模型中诱导肥大而不发生细胞增殖 使用各种完全不同的刺激（即激素和离子） 将能够确定单个起始事件是否是 细胞生长过程中常见的。 如果 Na-H 反向转运增加 一致发现，这很可能是事件 引发体内肾小管细胞肥大。