Dataset related to: Empagliflozin protects glomerular endothelial cell architecture in experimental diabetes through the VEGF-A/caveolin-1/PV-1 signaling pathway

The files contain all the dataset included in the manuscript divided by figures. Abstract<br> In addition to having blood glucose-lowering effects, inhibitors of sodium glucose cotransporter 2 (SGLT2) afford renoprotection in diabetes. We sought to investigate which components of the glomerular filtration barrier could be involved in the antiproteinuric and renoprotective effects of SGLT2 inhibition in diabetes. BTBR (black and tan, brachyuric) <em>ob/ob</em> mice that develop a type 2 diabetic nephropathy received a standard diet with or without empagliflozin for 10 weeks, starting at 8 weeks of age, when animals had developed albuminuria. Empagliflozin caused marked decreases in blood glucose levels and albuminuria but did not correct glomerular hyperfiltration. The protective effect of empagliflozin against albuminuria was not due to a reduction in podocyte damage as empagliflozin did not affect the larger podocyte filtration slit pore size nor the defective expression of nephrin and nestin. Empagliflozin<br> did not reduce the thickening of the glomerular basement membrane. In BTBR <em>ob/ob</em> mice, the most profound abnormality seen using electron microscopy was in the endothelial aspect of the glomerular capillary, with significant loss of endothelial fenestrations. Remarkably, empagliflozin ameliorated the subverted microvascular endothelial ultrastructure. Caveolae and bridging diaphragms between adjacent endothelial fenestrae were seen in diabetic mice and associated with increased expression of caveolin-1 and the appearance of PV-1. These endothelial abnormalities were limited by the SGLT2 inhibitor. Although no expression of SGLT2 was found in glomerular endothelial cells, SGLT2 was expressed in the podocytes of diabetic mice. VEGF-A, which is a known stimulus for endothelial caveolin-1 and PV-1, was increased in podocytes of BTBR <em>ob/ob</em> mice and normalized by SGLT2 inhibitor treatment.<br> Thus, empagliflozin’s protective effect on the glomerular endothelium of diabetic mice could be due to a limitation of the paracrine signaling of podocyte-derived VEGF-A that resulted in a reduction of the abnormal endothelial caveolin-1 and PV-1, with the consequent preservation of glomerular endothelial function and permeability.本文件包含手稿中按图表分类的全部数据集。 摘要：除具备降糖功效外，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂还可对糖尿病患者产生肾脏保护作用。本研究旨在探究糖尿病状态下，SGLT2抑制剂发挥抗蛋白尿及肾脏保护作用的潜在靶点，即肾小球滤过屏障的相关组分。 BTBR（黑棕短肢尿酸）<em>ob/ob</em>小鼠可自发2型糖尿病肾病，于8周龄已出现白蛋白尿的该类小鼠中，分别给予标准饲料与添加恩格列净（empagliflozin）的标准饲料，连续干预10周。 实验结果显示，恩格列净可显著降低血糖与白蛋白尿水平，但未能纠正肾小球高滤过状态。其对白蛋白尿的保护作用并非源于足细胞损伤的减轻：既未改变增宽的足细胞滤过裂隙孔径，也未影响nephrin与nestin的异常表达。此外，恩格列净亦未减轻肾小球基底膜增厚。 在BTBR <em>ob/ob</em>小鼠中，电子显微镜下观察到的最显著异常位于肾小球毛细血管内皮侧，表现为内皮窗孔显著减少。值得注意的是，恩格列净可改善糖尿病小鼠紊乱的微血管内皮超微结构。糖尿病小鼠可见内皮窗孔间的小窝（caveolae）与桥连隔膜，同时伴随窖蛋白-1（caveolin-1）表达升高以及PV-1的出现，而上述内皮异常可被SGLT2抑制剂所缓解。 尽管肾小球内皮细胞中未检测到SGLT2的表达，但糖尿病小鼠足细胞中可检测到SGLT2。作为已知的内皮窖蛋白-1与PV-1的刺激因子，血管内皮生长因子A（VEGF-A）在BTBR <em>ob/ob</em>小鼠足细胞中表达升高，而SGLT2抑制剂治疗可使其恢复至正常水平。 综上，恩格列净对糖尿病小鼠肾小球内皮的保护作用，可能是通过限制足细胞来源的VEGF-A的旁分泌信号通路实现，进而减少异常升高的内皮窖蛋白-1与PV-1表达，最终维持肾小球内皮功能并降低其通透性。