Dataset related to: Sirt3 deficiency promotes endothelial dysfunction and aggravates renal injury

The .xlsx file contains raw data related to the article "Sirt3 deficiency promotes endothelial dysfunction and aggravates renal injury. PLOS One. 2023 Oct 10;18(10):e0291909", available at the following link. Abstract Sirtuin 3 (SIRT3), the main deacetylase of mitochondria, modulates the acetylation levels of substrates governing metabolism and oxidative stress. In the kidney, we showed that SIRT3 affects the proper functioning of high energy-demanding cells, such as tubular cells and podocytes. Less is known about the role of SIRT3 in regulating endothelial cell function and its impact on the progression of kidney disease. Here, we found that whole body Sirt3-deficient mice exhibited reduced renal capillary density, reflecting endothelial dysfunction, and VEGFA expression compared to wild-type mice. This was paralleled by activation of hypoxia signaling, upregulation of HIF-1α and Angiopietin-2, and oxidative stress increase. These alterations did not result in kidney disease. However, when Sirt3-deficient mice were exposed to the nephrotoxic stimulus Adriamycin (ADR) they developed aggravated endothelial rarefaction, altered VEGFA signaling, and higher oxidative stress compared to wild-type mice receiving ADR. As a result, ADR-treated Sirt3-deficient mice experienced a more severe injury with exacerbated albuminuria, podocyte loss and fibrotic lesions. These data suggest that SIRT3 is a crucial regulator of renal vascular homeostasis and its dysregulation is a predisposing factor for kidney disease. By extension, our findings indicate SIRT3 as a pharmacologic target in progressive renal disease whose treatments are still imperfect.该.xlsx文件包含与论文《Sirt3缺陷促进内皮功能障碍并加重肾损伤》[发表于PLOS One, 2023年10月10日;18(10):e0291909]相关的原始数据，可通过以下链接获取。 摘要 Sirtuin 3（SIRT3）作为线粒体主要的去乙酰化酶，可调控参与代谢与氧化应激过程的底物乙酰化水平。在肾脏组织中，本团队已证实SIRT3能够维持高能量需求细胞（如肾小管细胞与足细胞）的正常功能。目前学界对于SIRT3在调控内皮细胞功能中的作用，及其对肾病进展的影响仍知之甚少。本研究发现，与野生型小鼠相比，全身Sirt3基因缺陷小鼠的肾毛细血管密度降低，这一表型反映了内皮功能障碍，同时其血管内皮生长因子A（VEGFA）的表达水平也有所下降。与此同时，该类小鼠还出现了缺氧信号通路激活、缺氧诱导因子-1α（HIF-1α）与血管生成素-2（Angiopietin-2）表达上调，以及氧化应激增强的现象。上述改变并未直接引发肾脏疾病。然而，当Sirt3基因缺陷小鼠暴露于肾毒性刺激药物阿霉素（Adriamycin, ADR）时，与接受ADR处理的野生型小鼠相比，其内皮细胞稀疏程度进一步加重，血管内皮生长因子A信号通路出现异常，且氧化应激水平更高。最终，经ADR处理的Sirt3基因缺陷小鼠肾损伤更为严重，表现为蛋白尿加剧、足细胞丢失与纤维化病变。上述数据表明，SIRT3是肾脏血管稳态的关键调控因子，其功能失调是肾病的易感危险因素。进一步引申来看，本研究结果提示SIRT3可作为进行性肾病的药理学靶点，而目前针对此类肾病的临床治疗手段仍不完善。