Departement of Pediatrics, Division of Pediatric Nephrology, University of Florida, 32610, United States of America.
Department of Physiology and Aging, College of Medicine, University of Florida, 32610, United States of America.
Biochim Biophys Acta Mol Basis Dis. 2024 Jun;1870(5):167096. doi: 10.1016/j.bbadis.2024.167096. Epub 2024 Mar 16.
Unilateral nephrectomy, a procedure reducing kidney mass, triggers a compensatory response in the remaining kidney, increasing its size and function to maintain a normal glomerular filtration rate (GFR). Recent research has highlighted the role of extracellular vesicles (EVs) in renal physiology and disease, although their involvement in unilateral nephrectomy has been underexplored. In this study, unilateral nephrectomy was performed on young mice, and urinary extracellular vesicles (uEVs) characterization and cargo were analyzed. Kidney volume increased significantly post-nephrectomy, demonstrating compensatory hypertrophy. Serum creatinine, cystatin C, and urinary electrolytes concentrations were similar in both nephrectomized and control groups. Western blot analysis revealed upregulation of sodium-glucose cotransporter 2 (SGLT2) and sodium chloride cotransporter (NCC), and downregulation of sodium‑potassium-chloride co-transporter (NKCC2) and epithelial sodium channel (ENaC) in the nephrectomized group. Metabolomic analysis of uEVs showed an enrichment of certain metabolites, including citrate and stachydrine. Interestingly, uEVs from the nephrectomized group demonstrated a protective effect, downregulating signal transducer and activator of transcription 3 (STAT3) and reducing reactive oxygen species (ROS) in renal proximal cells, compared to uEVs from the control group. This study suggests that uEVs contain bioactive components capable of inducing protective, anti-inflammatory, anti-fibrinolytic, and antioxidative effects in renal cells. These findings contribute to our understanding of uEVs' role in renal compensatory mechanisms after unilateral nephrectomy and may hold promise for future therapeutic interventions in renal diseases.
单侧肾切除术会减少肾脏的质量，从而触发剩余肾脏的代偿反应，增加其大小和功能以维持正常的肾小球滤过率（GFR）。最近的研究强调了细胞外囊泡（EVs）在肾脏生理学和疾病中的作用，尽管它们在单侧肾切除术后的作用尚未得到充分探索。在这项研究中，对年轻小鼠进行了单侧肾切除术，并分析了尿细胞外囊泡（uEVs）的特征和货物。肾切除术后，肾脏体积明显增加，表明代偿性肥大。血清肌酐、胱抑素 C 和尿电解质浓度在肾切除组和对照组之间相似。Western blot 分析显示，肾切除组中钠-葡萄糖共转运蛋白 2（SGLT2）和氯化钠共转运蛋白（NCC）上调，而钠-钾-氯共转运蛋白（NKCC2）和上皮钠通道（ENaC）下调。uEVs 的代谢组学分析显示某些代谢物（包括柠檬酸和莨菪亭）富集。有趣的是，与对照组相比，肾切除组的 uEVs 表现出保护作用，下调了信号转导和转录激活因子 3（STAT3）并减少了肾近端细胞中的活性氧（ROS）。这项研究表明，uEVs 包含能够在肾细胞中诱导保护、抗炎、抗纤维蛋白溶解和抗氧化作用的生物活性成分。这些发现有助于我们理解 uEVs 在单侧肾切除术后肾脏代偿机制中的作用，并可能为肾脏疾病的未来治疗干预提供新的思路。
