Mechanism Of Renal Tubular Cell Injury

肾小管细胞损伤机制

• 批准号: 6892815
• 负责人: JOHN H SCHWARTZ
• 金额: $ 31.19万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6892815
• 关键词: acute renal failure; adenosine triphosphate; apoptosis; basement membrane; cadherins; cell cell interaction; cellular pathology; gene expression; lithium; nuclear factor kappa beta; phosphorylation; regeneration; renal ischemia /hypoxia; renal tubule; tissue /cell culture; transcription factor; transfection

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.

描述（由申请人提供）： 目标：本申请的总体目标是检查 13-catenin-Lef 信号通路在导致与急性肾损伤相关的基因表达改变中的作用，并阐明该通路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：检验 ATP 消耗-补充会激活培养的近端肾小管细胞中的 Beta-catenin Lef 通路的假设。 具体目标 2：检验我们的假设，即 ATP 耗尽-补充会导致 β-catenin-Lef 介导的基因表达激活。 具体目标 3：检验我们的假设，即 Beta-catenin-lef-1 通路单独或与 NF-kappB 联合抑制 ATP 耗尽-补充诱导的细胞凋亡。 长期目标：阐明急性肾衰竭（ARF）恢复和修复过程中涉及的机制。 意义：阐明恢复和修复所涉及的机制可能会带来深入的见解，从而有助于开发促进 ARF 恢复的治疗干预措施。

项目成果

ATP depletion of tubular cells causes dissociation of the zonula adherens and nuclear translocation of beta-catenin and LEF-1.

• DOI: 10.1097/01.asn.0000012609.22035.44
• 发表时间: 2002-05
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: V. Price;C. Reed;W. Lieberthal;J. Schwartz

Role of mitofusin 2 in the renal stress response.

• DOI: 10.1371/journal.pone.0031074
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gall JM;Wang Z;Liesa M;Molina A;Havasi A;Schwartz JH;Shirihai O;Borkan SC;Bonegio RG
• 通讯作者: Bonegio RG

Induction of heat shock protein 70 inhibits ischemic renal injury.

• DOI: 10.1038/ki.2010.527
• 发表时间: 2011-04
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Wang Z;Gall JM;Bonegio RG;Havasi A;Hunt CR;Sherman MY;Schwartz JH;Borkan SC
• 通讯作者: Borkan SC

Hexokinase regulates Bax-mediated mitochondrial membrane injury following ischemic stress.

• DOI: 10.1038/ki.2010.532
• 发表时间: 2011-06
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Gall JM;Wong V;Pimental DR;Havasi A;Wang Z;Pastorino JG;Bonegio RG;Schwartz JH;Borkan SC
• 通讯作者: Borkan SC