Extracellular vesicles regulate purinergic signaling and epithelial sodium channel expression in renal collecting duct cells

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dc.contributor.authorLamus, Eric R. Barros
dc.contributor.authorCarotti, Valentina
dc.contributor.authorde Vries, Christine R. S.
dc.contributor.authorWitsel, Femke
dc.contributor.authorArntz, Onno J.
dc.contributor.authorvan de Loo, Fons A. J.
dc.contributor.authorCarvajal, Cristian A.
dc.contributor.authorBindels, Rene J. M.
dc.contributor.authorHoenderop, Joost G. J.
dc.contributor.authorRigalli, Juan P.
dc.date.accessioned2025-01-20T22:21:03Z
dc.date.available2025-01-20T22:21:03Z
dc.date.issued2021
dc.description.abstractPurinergic 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.
dc.fuente.origenWOS
dc.identifier.doi10.1096/fj.202002559R
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.urihttps://doi.org/10.1096/fj.202002559R
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94640
dc.identifier.wosidWOS:000645260100031
dc.issue.numero5
dc.language.isoen
dc.revistaFaseb journal
dc.rightsacceso restringido
dc.subjectaldosterone
dc.subjectepithelial sodium channel
dc.subjectexosomes
dc.subjectextracellular vesicles
dc.subjectpurinergic signaling
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleExtracellular vesicles regulate purinergic signaling and epithelial sodium channel expression in renal collecting duct cells
dc.typeartículo
dc.volumen35
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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