Extracellular vesicle-bound DNA in urine is indicative of kidney allograft injury

Sedej, Ivana (avtor), Štalekar, Maja (avtor), Tušek-Žnidarič, Magda (avtor), Goričar, Katja (avtor), Kojc, Nika (avtor), Kogovšek, Polona (avtor), Dolžan, Vita (avtor), Arnol, Miha (avtor), Lenassi, Metka (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: DNA, cell-free DNA, donor-derived DNA, extracellular vesicles, kidney allograft injury, kidney allograft rejection, liquid biopsy, urine
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: 23 str.
• Številčenje: Vol. 11, iss. 9, art. e12268
• PID: 20.500.12556/RUL-153979
• UDK: 616.6
• ISSN pri članku: 2001-3078
• DOI: 10.1002/jev2.12268
• COBISS.SI-ID: 123229443
• Datum objave v RUL: 17.01.2024

Gradivo je del revije

• Naslov: Journal of extracellular vesicles
• Založnik: Wiley, International Society for Extracellular Vesicles
• ISSN: 2001-3078
• COBISS.SI-ID: 9796948

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: DNK, DNK, pridobljena iz darovalca, zunajcelični vezikli