Browsing by Author "Bindels, Rene J. M."

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    Comparing Approaches to Normalize, Quantify, and Characterize Urinary Extracellular Vesicles
    (2021) Blijdorp, Charles J.; Tutakhel, Omar A. Z.; Hartjes, Thomas A.; van den Bosch, Thierry P. P.; van Heugten, Martijn H.; Rigalli, Juan Pablo; Willemsen, Rob; Musterd-Bhaggoe, Usha M.; Barros, Eric R.; Carles-Fontana, Roger; Carvajal, Cristian A.; Arntz, Onno J.; van de Loo, Fons A. J.; Jenster, Guido; Clahsen-van Groningen, Marian C.; Cuevas, Cathy A.; Severs, David; Fenton, Robert A.; van Royen, Martin E.; Hoenderop, Joost G. J.; Bindels, Rene J. M.; Hoorn, Ewout J.
    Background: Urinary extracellular vesicles (uEVs) are a promising source for biomarker discovery, but optimal approaches for normalization, quantification, and characterization in spot urines are unclear.
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    Extracellular vesicles regulate purinergic signaling and epithelial sodium channel expression in renal collecting duct cells
    (2021) Lamus, Eric R. Barros; Carotti, Valentina; de Vries, Christine R. S.; Witsel, Femke; Arntz, Onno J.; van de Loo, Fons A. J.; Carvajal, Cristian A.; Bindels, Rene J. M.; Hoenderop, Joost G. J.; Rigalli, Juan P.
    Purinergic signaling regulates several renal physiological and pathophysiological processes. Extracellular vesicles (EVs) are nanoparticles released by most cell types, which, in non-renal tissues, modulate purinergic signaling. The aim of this study was to investigate the effect of EVs from renal proximal tubule (HK2) and collecting duct cells (HCD) on intra-and intersegment modulation of extracellular ATP levels, the underlying molecular mechanisms, and the impact on the expression of the alpha subunit of the epithelial sodium channel (alpha ENaC). HK2 cells were exposed to HK2 EVs, while HCD cells were exposed to HK2 and HCD EVs. Extracellular ATP levels and alpha ENaC expression were measured by chemiluminescence and -qRT-PCR, respectively. ATPases in EV populations were identified by mass spectrometry. The effect of aldosterone was assessed using EVs from aldosterone-treated cells and urinary EVs (uEVs) from primary aldosteronism (PA) patients. HK2 EVs downregulated ectonucleoside-triphosphate-diphosphohydrolase-1 (ENTPD1) expression, increased extracellular ATP and downregulated alpha ENaC expression in HCD cells. ENTPD1 downregulation could be attributed to increased miR-205-3p and miR-505 levels. Conversely, HCD EVs decreased extracellular ATP levels and upregulated alpha ENaC expression in HCD cells, probably due to enrichment of 14-3-3 isoforms with ATPase activity. Pretreatment of donor cells with aldosterone or exposure to uEVs from PA patients enhanced the effects on extracellular ATP and alpha ENaC expression. We demonstrated inter-and intrasegment modulation of renal purinergic signaling by EVs. Our findings postulate EVs as carriers of information along the renal tubules, whereby processes affecting EV release and/or cargo may impact on purinergically regulated processes.
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    Proteomic Profile of Urinary Extracellular Vesicles Identifies AGP1 as a Potential Biomarker of Primary Aldosteronism
    (2021) Barros, Eric R.; Rigalli, Juan Pablo; Tapia-Castillo, Alejandra; Vecchiola, Andrea; Young, Morag J.; Hoenderop, Joost G. J.; Bindels, Rene J. M.; Fardella, Carlos E.; Carvajal, Cristian A.
    Context: Primary aldosteronism (PA) represents 6% to 10% of all essential hypertension patients and is diagnosed using the aldosterone-to-renin ratio (ARR) and confirmatory studies. The complexity of PA diagnosis encourages the identification of novel PA biomarkers. Urinary extracellular vesicles (uEVs) are a potential source of biomarkers, considering that their cargo reflects the content of the parent cell.