Mechanism Of Renal Tubular Cell Injury

描述（由申请人提供）：目的：本申请的总体目的是检查13-连环蛋白-Lef信号传导途径在促进与急性肾损伤相关的基因表达改变中的作用，并阐明该途径在调节与肾功能恢复相关的事件中的作用。 具体目标每个具体目标将测试三个相互关联的假设之一： 具体目标1：验证ATP消耗-补充激活培养的近端肾小管细胞中β-连环蛋白Lef途径的假设。 具体目标2：检验我们的假设，即ATP耗竭-补充导致β-连环蛋白-Lef介导的基因表达激活。 具体目标3：为了验证我们的假设，即β-连环蛋白-lef-1通路单独或与NF-κ B联合抑制ATP耗竭-再灌注诱导的细胞凋亡。 长期目标：阐明急性肾功能衰竭（ARF）恢复和修复过程中的机制。 重要性：阐明涉及恢复和修复的机制可能有助于促进ARF恢复的治疗干预措施的发展。

DESCRIPTION (provided by applicant): Goals: The overall goals of this application are to examine the role of a the 13-catenin-Lef signaling pathway in contributing to the alterations in gene expression associated with acute renal injury and to elucidate the role of this pathway in modulating events associated with recovery of renal function. Specific aims Each specific aims will test one of three interrelated hypotheses: Specific aim 1: To test the hypothesis that ATP depletion-repletion activates the Beta-catenin Lef pathway in cultured proximal tubular cells. Specific aim 2: To examine our hypothesis that ATP depletion-repletion results in beta-catenin-Lef mediated activation of gene expression. Specific aim 3: To test our hypothesis that the Beta-catenin-lef-1 pathway alone or in association with NF-kappB inhibits apoptosis induced by ATP depletion-repletion. Long-term goals: To elucidate the mechanisms involved in the process of recovery and repair from acute renal failure (ARF). Significance: Elucidation of the mechanisms involved in recovery and repair may lead to insight that facilitate the development of therapeutic interventions that promote recovery from ARF.