Urinary Extracellular Vesicles Carrying Klotho Improve the Recovery of Renal Function in an Acute Tubular Injury Model
| العنوان: | Urinary Extracellular Vesicles Carrying Klotho Improve the Recovery of Renal Function in an Acute Tubular Injury Model |
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| المؤلفون: | Cecilia Pastorino, Jordi Molina, Cristina Grange, Paul D. Robbins, Benedetta Bussolati, Elli Papadimitriou, Ryan D. O’Kelly, Laura J. Niedernhofer, Veronica Dimuccio, Giovanni Camussi |
| المصدر: | Molecular Therapy |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | engineering, Endogeny, Kidney Function Tests, urologic and male genital diseases, Mice, 0302 clinical medicine, Drug Discovery, Medicine, Klotho, Glucuronidase, 0303 health sciences, vesicles, Acute kidney injury, renal regeneration, Acute Kidney Injury, Immunohistochemistry, female genital diseases and pregnancy complications, microRNAs, Kidney Tubules, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cytokines, Molecular Medicine, Original Article, Inflammation Mediators, damage, Urinary system, Renal function, Extracellular Vesicles, 03 medical and health sciences, AKI, injury markers, mesenchymal stem cells, urinary exosomes, microRNA, Genetics, Animals, Fibroblast, Klotho Proteins, Molecular Biology, 030304 developmental biology, Pharmacology, business.industry, Mesenchymal stem cell, medicine.disease, Cancer research, business, Biomarkers |
| الوصف: | Acute kidney injury, defined by a rapid deterioration of renal function, is a common complication in hospitalized patients. Among the recent therapeutic options, the use of extracellular vesicles (EVs) is considered a promising strategy. Here we propose a possible therapeutic use of renal-derived EVs isolated from normal urine (urine-derived EVs [uEVs]) in a murine model of acute injury generated by glycerol injection. uEVs accelerated renal recovery, stimulating tubular cell proliferation, reducing the expression of inflammatory and injury markers, and restoring endogenous Klotho loss. When intravenously injected, labeled uEVs localized within injured kidneys and transferred their microRNA cargo. Moreover, uEVs contained the reno-protective Klotho molecule. Murine uEVs derived from Klotho null mice lost the reno-protective effect observed using murine EVs from wild-type mice. This was regained when Klotho-negative murine uEVs were reconstituted with recombinant Klotho. Similarly, ineffective fibroblast EVs acquired reno-protection when engineered with human recombinant Klotho. Our results reveal a novel potential use of uEVs as a new therapeutic strategy for acute kidney injury, highlighting the presence and role of the reno-protective factor Klotho. Graphical Abstract In this issue, Grange et al. (2019) show the therapeutic activity of urine-derived EVs in a murine model of acute kidney injury and highlight the presence and indispensable role of the reno-protective factor Klotho carried by uEVs. The regenerative capacity of EVs engineered with human recombinant Klotho is also proposed. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e726d5aaafe2fd3a659f6d02da884a3 http://hdl.handle.net/2318/1726934 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9e726d5aaafe2fd3a659f6d02da884a3 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |