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尿足细胞来源迁移小体定量用于肾脏疾病的诊断。

Quantification of urinary podocyte-derived migrasomes for the diagnosis of kidney disease.

机构信息

Department of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, China.

出版信息

J Extracell Vesicles. 2024 Jun;13(6):e12460. doi: 10.1002/jev2.12460.

Abstract

Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non-invasive source for disease diagnosis through liquid biopsy. In this investigation, we introduce a streamlined and effective approach for the capture and quantitative assessment of migrasomes, employing wheat germ agglutinin (WGA)-coated magnetic beads and flow cytometry (referred to as WBFC). Subsequently, we examined the levels of migrasomes in the urine of kidney disease (KD) patients with podocyte injury and healthy volunteers using WBFC. The outcomes unveiled a substantial increase in urinary podocyte-derived migrasome concentrations among individuals with KD with podocyte injury compared to the healthy counterparts. Notably, the urinary podocyte-derived migrasomes were found to express an abundant quantity of phospholipase A2 receptor (PLA2R) proteins. The presence of PLA2R proteins in these migrasomes holds promise for serving as a natural antigen for the quantification of autoantibodies against PLA2R in the serum of patients afflicted by membranous nephropathy. Consequently, our study not only pioneers a novel technique for the isolation and quantification of migrasomes but also underscores the potential of urinary migrasomes as a promising biomarker for the early diagnosis of KD with podocyte injury.

摘要

迁移小体是一类新近发现的细胞外微囊泡,直径范围在 500 至 3000nm 之间。它们由迁移细胞释放,并携带有多种 RNA 和蛋白质。迁移小体可在血清和尿液等体液中轻易被识别,这使得它们成为液体活检中用于疾病诊断的一种极具价值的非侵入性来源。在本研究中,我们引入了一种简化且高效的方法,用于捕获和定量评估迁移小体,该方法采用麦胚凝集素(WGA)包被的磁珠和流式细胞术(简称 WBFC)。随后,我们使用 WBFC 检测了具有足细胞损伤的肾病(KD)患者和健康志愿者尿液中的迁移小体水平。结果显示,与健康对照组相比,具有足细胞损伤的 KD 患者尿液中足细胞衍生的迁移小体浓度显著增加。值得注意的是,这些迁移小体表达大量的磷脂酶 A2 受体(PLA2R)蛋白。这些迁移小体中 PLA2R 蛋白的存在为定量检测膜性肾病患者血清中针对 PLA2R 的自身抗体提供了一种天然抗原。因此,本研究不仅开创了一种分离和定量迁移小体的新技术,还强调了尿液迁移小体作为早期诊断足细胞损伤型 KD 的有前途的生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f189/11162892/0ce4e0d52c45/JEV2-13-e12460-g001.jpg

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