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      Quantification of urinary podocyte‐derived migrasomes for the diagnosis of kidney disease

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          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.

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          Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI. Funding Bill & Melinda Gates Foundation.
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            Discovery of the migrasome, an organelle mediating release of cytoplasmic contents during cell migration

            Cells communicate with each other through secreting and releasing proteins and vesicles. Many cells can migrate. In this study, we report the discovery of migracytosis, a cell migration-dependent mechanism for releasing cellular contents, and migrasomes, the vesicular structures that mediate migracytosis. As migrating cells move, they leave long tubular strands, called retraction fibers, behind them. Large vesicles, which contain numerous smaller vesicles, grow on the tips and intersections of retraction fibers. These fibers, which connect the vesicles with the main cell body, eventually break, and the vesicles are released into the extracellular space or directly taken up by surrounding cells. Since the formation of these vesicles is migration-dependent, we named them “migrasomes”. We also found that cytosolic contents can be transported into migrasomes and released from the cell through migrasomes. We named this migration-dependent release mechanism “migracytosis”.
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              Mitocytosis, a migrasome-mediated mitochondrial quality-control process

              Damaged mitochondria need to be cleared to maintain the quality of the mitochondrial pool. Here, we report mitocytosis, a migrasome-mediated mitochondrial quality-control process. We found that, upon exposure to mild mitochondrial stresses, damaged mitochondria are transported into migrasomes and subsequently disposed of from migrating cells. Mechanistically, mitocytosis requires positioning of damaged mitochondria at the cell periphery, which occurs because damaged mitochondria avoid binding to inward motor proteins. Functionally, mitocytosis plays an important role in maintaining mitochondrial quality. Enhanced mitocytosis protects cells from mitochondrial stressor-induced loss of mitochondrial membrane potential (MMP) and mitochondrial respiration; conversely, blocking mitocytosis causes loss of MMP and mitochondrial respiration under normal conditions. Physiologically, we demonstrate that mitocytosis is required for maintaining MMP and viability in neutrophils in vivo. We propose that mitocytosis is an important mitochondrial quality-control process in migrating cells, which couples mitochondrial homeostasis with cell migration.
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                Author and article information

                Contributors
                liuzhihong@nju.edu.cn
                kzen@nju.edu.cn
                ygyuan@njmu.edu.cn
                hwliang@nju.edu.cn
                Journal
                J Extracell Vesicles
                J Extracell Vesicles
                10.1002/(ISSN)2001-3078
                JEV2
                Journal of Extracellular Vesicles
                John Wiley and Sons Inc. (Hoboken )
                2001-3078
                09 June 2024
                June 2024
                : 13
                : 6 ( doiID: 10.1002/jev2.v13.6 )
                : e12460
                Affiliations
                [ 1 ] Department of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology China Pharmaceutical University Nanjing China
                [ 2 ] State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science Nanjing University Nanjing China
                [ 3 ] Department of Nephrology The First Affiliated Hospital of Nanjing Medical University Nanjing China
                [ 4 ] National Clinical Research Center of Kidney Diseases, Jinling Hospital Nanjing University School of Medicine Nanjing China
                [ 5 ] Cancer Center, Faculty of Health Sciences University of Macau Macau SAR China
                Author notes
                [*] [* ] Correspondence

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

                Email: hwliang@ 123456nju.edu.cn

                Yanggang Yuan, Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

                Email: ygyuan@njmu.edu.cn

                Ke Zen, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, Chian.

                Email: kzen@nju.edu.cn

                Zhihong Liu, National Clinical Research Center of Kidney Disease, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

                Email: liuzhihong@nju.edu.cn

                Author information
                https://orcid.org/0000-0003-1086-3718
                Article
                JEV212460
                10.1002/jev2.12460
                11162892
                38853287
                de042ef9-8c98-41e2-953b-4433c141692f
                © 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Page count
                Figures: 5, Tables: 4, Pages: 19, Words: 11573
                Funding
                Funded by: The National Natural Science Foundation of China
                Award ID: 31801088
                Award ID: 32170783
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                June 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.4 mode:remove_FC converted:09.06.2024

                diagnosis,kidney disease,migrasomes,podocyte,quantification,urinary

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