| Title: | Extracellular vesicle-bound DNA in urine is indicative of kidney allograft injury |
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| Authors: | ID Sedej, Ivana (Author)
ID Štalekar, Maja (Author)
ID Tušek-Žnidarič, Magda (Author)
ID Goričar, Katja (Author)
ID Kojc, Nika (Author)
ID Kogovšek, Polona (Author)
ID Dolžan, Vita (Author)
ID Arnol, Miha (Author)
ID Lenassi, Metka (Author) |
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| Files: |  URL - Source URL, visit https://onlinelibrary.wiley.com/doi/10.1002/jev2.12268
 PDF - Presentation file, download (7,03 MB)
MD5: CFBC3A406854D04F5AF506E3F8A7D2A8
URL - Source URL, visit https://doi.org/10.1002/jev2.12268
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | Extracellular vesicle-bound DNA (evDNA) is an understudied extracellular vesicle (EV) cargo, particularly in cancer-unrelated research. Although evDNA has been detected in urine, little is known about its characteristics, localization, and biomarker potential for kidney pathologies. To address this, we enriched EVs from urine of well-characterized kidney transplant recipients undergoing allograft biopsy, characterized their evDNA and its association to allograft injury. The SEC-based method enriched pure EVs from urine of kidney transplant recipients, regardless of the allograft injury. Urinary evDNA represented up to 29.2 ± 8% (mean ± SD) of cell-free DNA (cfDNA) and correlated with cfDNA in several characteristics but was less fragmented (P < 0.001). Importantly, using DNase treatment and immunogold labelling TEM, we demonstrated that evDNA was bound to the surface of urinary EVs. Normalised evDNA yield (P = 0.042) and evDNA copy number (P = 0.027) significantly differed between patients with normal histology, rejection injury and non-rejection injury, the later groups having significantly larger uEVs (mean diameter, P = 0.045) and more DNA bound per uEV. ddDNA is detectable in uEV samples of kidney allograft recipients, but its quantity is highly variable. In a proof-of-principle study, several evDNA characteristics correlated with clinical and histological parameters (P = 0.040), supporting that the potential of evDNA as a biomarker for kidney allograft injury should be further investigated. |
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| Keywords: | DNA, donor-derived DNA, extracellular vesicles |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 23.09.2022 |
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| Year of publishing: | 2022 |
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| Number of pages: | str. 1-23 |
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| Numbering: | Vol. 11, iss. 9 |
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| PID: | 20.500.12556/DiRROS-21562  |
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| UDC: | 616.6 |
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| ISSN on article: | 2001-3078 |
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| DOI: | 10.1002/jev2.12268 |
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| COBISS.SI-ID: | 123229443 |
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| Note: | Soavtorji: Maja Štalekar, Magda Tušek Žnidarič, Katja Goričar, Nika Kojc, Polona Kogovšek, Vita Dolžan, Miha Arnol, Metka Lenassi;
Nasl. z nasl. zaslona;
Opis vira z dne 28. 9. 2022;
Št. članka: e12268;
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| Publication date in DiRROS: | 26.02.2025 |
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| Views: | 633 |
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| Downloads: | 517 |
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