Grossini Elena, Quaglia Marco, Prenna Stefania, Stasi Alessandra, Franzin Rossana, Castellano Giuseppe, Remorgida Valentino, Libretti Alessandro, Venkatesan Sakthipriyan, Smirne Carlo, Merlotti Guido, Aquino Carmen Imma, Bruno Stefania, Camussi Giovanni, Surico Daniela, Cantaluppi Vincenzo
Laboratory of Physiology, Department of Translational Medicine (DIMET), University of Piemonte Orientale (UPO), 28100 Novara, Italy.
AGING Project Unit, Department of Translational Medicine (DIMET), University of Piemonte Orientale (UPO), 28100 Novara, Italy.
Int J Mol Sci. 2025 May 22;26(11):4962. doi: 10.3390/ijms26114962.
Extracellular vesicles (EVs) may play a role in preeclampsia (PE)-associated glomerular damage. We herein investigated the role of PE plasma EVs in triggering a detrimental crosstalk between glomerular endothelial cells (GEC) and podocytes (PODO). Clinical and laboratory variables were examined at T0 (diagnosis), T1 (delivery), and T2 (one month after delivery) in 36 PE patients and 17 age-matched controls. NanoSight and MACSPlex evaluated EV concentration, size, and phenotype. GEC and PODO were stimulated with plasma EVs to study viability, reactive oxygen species (ROS) production, permeability to albumin, endothelial-to-mesenchymal transition, and Endothelin-1 release. EV size and concentration were higher in PE than in healthy controls and in severe than in mild forms of disease. At T0, higher EV concentration correlated with proteinuria, blood pressure, uric acid, and liver enzyme levels. PE-EVs originated from leukocytes, endothelial cells, platelets, and the placenta and induced GEC and PODO damage as shown by the reduction of viability, increased ROS release, and albumin permeability. Co-culture experiments demonstrated that PE-EVs mediated a deleterious intraglomerular crosstalk through Endothelin-1 release from GEC able to down-regulate nephrin in PODO. In conclusion, we observed in PE plasma a peculiar pattern of EVs able to affect GEC and PODO functions and to induce proteinuria through Endothelin-1 involvement.
细胞外囊泡（EVs）可能在子痫前期（PE）相关的肾小球损伤中发挥作用。我们在此研究了PE血浆EVs在引发肾小球内皮细胞（GEC）和足细胞（PODO）之间有害串扰中的作用。在36例PE患者和17例年龄匹配的对照中，于T0（诊断时）、T1（分娩时）和T2（分娩后1个月）检查临床和实验室变量。纳米可视技术和多参数流式细胞术评估了EVs的浓度、大小和表型。用血浆EVs刺激GEC和PODO，以研究细胞活力、活性氧（ROS）产生、白蛋白通透性、内皮-间充质转化以及内皮素-1释放。PE患者的EVs大小和浓度高于健康对照，且重度患者高于轻度患者。在T0时，较高的EVs浓度与蛋白尿、血压、尿酸和肝酶水平相关。PE-EVs起源于白细胞、内皮细胞、血小板和胎盘，并诱导GEC和PODO损伤，表现为活力降低、ROS释放增加和白蛋白通透性增加。共培养实验表明，PE-EVs通过GEC释放内皮素-1介导肾小球内有害串扰，内皮素-1能够下调PODO中的nephrin。总之，我们在PE血浆中观察到一种特殊的EVs模式，其能够影响GEC和PODO功能，并通过内皮素-1参与诱导蛋白尿。
