Liang Wu, Carla C. Baan, Derek Reijerkerk, Dennis A. Hesselink, Karin Boer
{"title":"Urinary extracellular vesicles in healthy individuals: positive correlation between podocyte and tubular vesicles independent of kidney function","authors":"Liang Wu, Carla C. Baan, Derek Reijerkerk, Dennis A. Hesselink, Karin Boer","doi":"10.1101/2024.08.04.24311469","DOIUrl":null,"url":null,"abstract":"Urinary extracellular vesicles (uEVs) are promising non-invasive biomarkers for assessing renal physiology and disease. Focusing specifically on kidney-derived uEVs (kd-uEVs) rather than the overall uEV population may offer a more precise insight into kidney health. However, research distinguishing single kd-uEVs from various nephron segments and their relationship with kidney biology remains limited. Imaging flow cytometry (IFCM) can identify single kd-uEVs by labeling them with CD63 (a uEV marker) in combination with PODXL (a podocyte marker) or AQP2 (a tubular marker). This study investigated the correlations between CD63+ AQP2+ or PODXL+ kd-uEVs and kidney function. CD63+ AQP2+ and CD63+ PODXL+ uEVs were detected in urine compared to negative controls, including urine with detergent treatment or isotype staining and reagent-containing PBS. While no significant association was found between CD63+ AQP2+ or PODXL+ uEV concentration and kidney function, a significant correlation was observed between AQP2+ and PODXL+ uEV concentrations (Rho = 0.789, p < 0.001). This correlation could be explained by the colocalization of AQP2 and PODXL on CD63+ uEVs. In conclusion, our study is the first to demonstrate the colocalization of podocyte and tubular proteins on uEVs.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":"6 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv - Nephrology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.04.24311469","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Urinary extracellular vesicles (uEVs) are promising non-invasive biomarkers for assessing renal physiology and disease. Focusing specifically on kidney-derived uEVs (kd-uEVs) rather than the overall uEV population may offer a more precise insight into kidney health. However, research distinguishing single kd-uEVs from various nephron segments and their relationship with kidney biology remains limited. Imaging flow cytometry (IFCM) can identify single kd-uEVs by labeling them with CD63 (a uEV marker) in combination with PODXL (a podocyte marker) or AQP2 (a tubular marker). This study investigated the correlations between CD63+ AQP2+ or PODXL+ kd-uEVs and kidney function. CD63+ AQP2+ and CD63+ PODXL+ uEVs were detected in urine compared to negative controls, including urine with detergent treatment or isotype staining and reagent-containing PBS. While no significant association was found between CD63+ AQP2+ or PODXL+ uEV concentration and kidney function, a significant correlation was observed between AQP2+ and PODXL+ uEV concentrations (Rho = 0.789, p < 0.001). This correlation could be explained by the colocalization of AQP2 and PODXL on CD63+ uEVs. In conclusion, our study is the first to demonstrate the colocalization of podocyte and tubular proteins on uEVs.