Avtor/Urednik		Levstek, Tina; Mlinšek, Teo; Holcar, Marija; Goričar, Katja; Lenassi, Metka; Dolžan, Vita; Vujkovac, Bojan; Trebušak Podkrajšek, Katarina
Naslov		Urinary extracellular vesicles and their miRNA cargo in patients with Fabry nephropathy
Tip		članek
Vol. in št.		Letnik 12, št. 7
Leto izdaje		2021
Obseg		str. 1-15
ISSN		2073-4425 - Genes
Jezik		eng
Abstrakt		Current biomarkers of Fabry nephropathy lack sensitivity in detecting early kidney damageand do not predict progression of nephropathy. Urinary extracellular vesicles (uEVs) and theirmolecular cargo could reflect early changes in renal impairment as they are secreted by the cellslining the urinary tract. We aimed to conduct a proof-of-concept study to investigate whether analysisof uEV characteristics and expression of uEV-derived microRNAs (miRNAs) could be applicablein studies to predict the development and progression of nephropathy in Fabry disease. A totalof 20 Fabry patients were divided into two groups, depending on the presence of nephropathy.Chronological urine samples collected during 10-year follow-up were used for uEVs isolation withsize exclusion chromatography. Nanoparticle tracking analysis was used to determine concentrationand size of uEVs. We evaluated the expression of five uEV-derived miRNAs by qPCR (miR-23a-3p,miR-29a-3p, miR-30b-5p, miR-34a-5p, miR-200a-3p). There was no difference in the concentrationand size of uEVs between patients with and without nephropathy at last follow-up or longitudinally.However, we found increased expression of miR-29a-3p and miR-200a-3p in uEVs isolated fromchronological samples of patients with Fabry nephropathy. This may indicate an attempt by theorganism to prevent the progression of renal damage leading to end-stage renal disease as previouslyreported in type 1 diabetes. In addition, we found an increased expression of miR-30b-5p in the10-year period in uEVs of patients without renal dysfunction. miR-30b-5 was reported to have aprotective role in podocyte injury and may possibly be important in Fabry nephropathy. Thesefindings indicate that uEVs and their molecular cargo could be a promising target of studies focusingon elucidation of Fabry nephropathy. Nevertheless, total concentration and size of uEVs were neitherindicative of the presence nor progression of Fabry nephropathy, while the role of the analyzedmiRNAs in Fabry nephropathy progression was merely indicated and needs further in-depth studies.
Proste vsebinske oznake		Fabry nephropathy urinary extracellular vesicles miRNA expression Fabryjeva nefropatija urinski zunajcelični vezikli izražanje miRNA