Role of Nrf2 in aging kidney function

Nrf2在肾功能衰老中的作用

• 批准号: 9590483
• 负责人: Anees Ahmad Banday
• 金额: $ 45.9万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9590483
• 关键词: Adult; Affect; Age; Aging; American; Area; Body Fluids; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cell Culture System; Cell physiology; Co-Immunoprecipitations; Creatinine clearance measurement; Data; Economic Burden; Elderly; Electrophoretic Mobility Shift Assay; Environment; Enzymes; Event; Female; Fluorescence; Future; Genetic Transcription; Goals; Health; Healthcare Systems; Heart failure; Human; Impairment; Inbred F344 Rats; Kidney; Maintenance; Mediating; Mitochondria; Mitochondrial Proteins; Mitochondrial Proton-Translocating ATPases; Modeling; Molecular Target; Myocardial Infarction; Nuclear; Organ; Plasmids; Proteins; Rattus; Regulation; Renal function; Research; Respiration; Role; SP1 gene; Scheme; Small Interfering RNA; Sulforaphane; System; Universities; Western Blotting; age related; aged; aging population; cardiovascular health; expectation; graduate student; high risk; insight; kidney cell; male; meetings; molecular targeted therapies; novel; novel therapeutics; programs; restoration; targeted treatment; therapeutic target; transcription factor; undergraduate student

Project Summary: Kidney is a vital organ that by maintaining body fluid volume/composition maintains cardiovascular functions. Unfortunately kidney function reduces with age that contributes to cardiovascular disorders such as heart failure and myocardial infarction during aging. American aging population is increasing. It is projected that 72 million Americans will be 65 years and older by the year 2030. Considering increased vulnerability of the elderly for compromised kidney function and associated cardiovascular disorders, a major economic burden on the US healthcare system is inevitable. Despite past and ongoing research efforts, mechanisms contributing to reduced kidney function during aging remain largely unknown. Therefore, understanding mechanism(s) of age-related decline of kidney function is needed more than ever in order to identify new molecular therapeutic targets that can restore kidney function and reduce associated cardiovascular events in the elderly Americans. This proposal is a new step taken in that direction. Using aging rat model as well as kidney cell culture systems we propose to examine the interplay between transcriptional and mitochondrial systems. In particular the interaction between transcription factors Nrf2 and Sp1 and mitochondrial protein ATP-synthase will be examined. Our hypothesis is that the interaction between Nrf2, Sp1 and ATP-synthase is important for normal kidney function and loss/disruption of this key interaction contributes to decline in kidney function in aging. The expectation is that in future these molecules can be targeted therapeutically to restore kidney function and reduce associated cardiovascular events in aging.

项目概述：肾脏是一个重要的器官，通过维持体液体积/成分 维持心血管功能。不幸的是，肾功能随着年龄的增长而下降， 导致心血管疾病，如心力衰竭和心肌梗死， 衰老美国老龄化人口正在增加。预计将有7200万美国人 到2030年65岁以上的人。考虑到老年人更易受到 肾功能受损和相关的心血管疾病，这是一个主要的经济问题， 这对美国医疗体系的影响是不可避免的。尽管过去和正在进行的研究努力， 在衰老过程中导致肾功能下降的机制在很大程度上仍然未知。 因此，需要了解与年龄相关的肾功能下降的机制 以确定新的分子治疗靶点， 功能和减少相关的心血管事件在老年美国人。这项建议是 朝着这个方向迈出了新的一步。利用衰老大鼠模型和肾细胞培养系统 我们建议检查转录和线粒体系统之间的相互作用。在 特别是转录因子Nrf 2和Sp1与线粒体蛋白的相互作用 将检查ATP合酶。我们的假设是，Nrf 2，Sp1和 ATP合酶对正常肾功能和这种关键相互作用的丧失/破坏很重要 导致肾功能在衰老过程中下降。预计在未来， 分子可以在治疗上被靶向以恢复肾功能并减少相关的 心血管事件