Regulation of tubular metabolism, senescence and renal regeneration by coagulation proteases in the context of diabetic kidney disease (B07)

糖尿病肾病中凝血蛋白酶对肾小管代谢、衰老和肾脏再生的调节 (B07)

• 批准号: 408076869
• 金额: --
• 依托单位: Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/408076869?language=en
• 关键词: Regulation; tubular; metabolism; senescence; renal

The „metabolic memory” is an unsolved medical problem. We postulate that (i) the metabolic memory is based on epigenetically fixed gene dysregulation with associated senescence, sterile inflammation, and reactive metabolites, and (ii) that these changes are controlled by endothelial dysfunction and an associated impaired signal transduction by coagulation proteases. Using innovative mouse models and methods, we intend to clarify the causal significance of epigenetically fixed senescence and its regula-tion by the coagulation system and, based on this, to identify new therapeutic targets.

“代谢性记忆”是一个尚未解决的医学问题。我们假设：(i)代谢记忆是基于表观遗传固定的基因失调，与衰老、无菌炎症和反应性代谢物相关，（ii）这些变化是由内皮功能障碍和凝血蛋白酶相关的信号转导受损控制的。利用创新的小鼠模型和方法，我们打算阐明表观遗传固定衰老的因果意义及其由凝血系统调节，并在此基础上确定新的治疗靶点。