Circulating extracellular vesicles of patients with steroid-sensitive nephrotic syndrome have higher RAC1 and induce recapitulation of nephrotic syndrome phenotype in podocytes

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buir.contributor.authorKara Eroğlu, Fehime
buir.contributor.authorYazar, Volkan
buir.contributor.authorYıldırım, Muzaffer
buir.contributor.authorYıldırım, Tuğçe
buir.contributor.authorTuray, Nilsu
buir.contributor.authorGürsel, İhsan
buir.contributor.orcidKara Eroğlu, Fehime|0000-0003-2364-4282
buir.contributor.orcidYazar, Volkan|0000-0003-3861-0181
buir.contributor.orcidTuray, Nilsu|0000-0002-6365-3469
buir.contributor.orcidGürsel, İhsan|0000-0003-3761-1166
dc.citation.epageF673en_US
dc.citation.issueNumber5en_US
dc.citation.spageF659en_US
dc.citation.volumeNumber321en_US
dc.contributor.authorKara Eroğlu, Fehime
dc.contributor.authorYazar, Volkan
dc.contributor.authorGuler, Ulku
dc.contributor.authorYıldırım, Muzaffer
dc.contributor.authorYıldırım, Tuğçe
dc.contributor.authorGungor, Tulin
dc.contributor.authorCelikkaya, Evra
dc.contributor.authorKarakaya, Deniz
dc.contributor.authorTuray, Nilsu
dc.contributor.authorCiftci Dede, Eda
dc.contributor.authorKorkusuz, Petek
dc.contributor.authorSalih, Bekir
dc.contributor.authorBulbul, Mehmet
dc.contributor.authorGürsel, İhsan
dc.date.accessioned2022-02-08T08:52:47Z
dc.date.available2022-02-08T08:52:47Z
dc.date.issued2021-11-09
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractSince previous research suggests a role of a circulating factor in the pathogenesis of steroid-sensitive nephrotic syndrome (NS), we speculated that circulating plasma extracellular vesicles (EVs) are a candidate source of such a soluble mediator. Here, we aimed to characterize and try to delineate the effects of these EVs in vitro. Plasma EVs from 20 children with steroid-sensitive NS in relapse and remission, 10 healthy controls, and 6 disease controls were obtained by serial ultracentrifugation. Characterization of these EVs was performed by electron microscopy, flow cytometry, and Western blot analysis. Major proteins from plasma EVs were identified via mass spectrometry. Gene Ontology classification analysis and Ingenuity Pathway Analysis were performed on selectively expressed EV proteins during relapse. Immortalized human podocyte culture was used to detect the effects of EVs on podocytes. The protein content and particle number of plasma EVs were significantly increased during NS relapse. Relapse NS EVs selectively expressed proteins that involved actin cytoskeleton rearrangement. Among these, the level of RAC-GTP was significantly increased in relapse EVs compared with remission and disease control EVs. Relapse EVs were efficiently internalized by podocytes and induced significantly enhanced motility and albumin permeability. Moreover, relapse EVs induced significantly higher levels of RAC-GTP and phospho-p38 and decreased the levels of synaptopodin in podocytes. Circulating relapse EVs are biologically active molecules that carry active RAC1 as cargo and induce recapitulation of the NS phenotype in podocytes in vitro.en_US
dc.identifier.doi10.1152/ajprenal.00097.2021en_US
dc.identifier.eissn1522-1466
dc.identifier.issn1931-857X
dc.identifier.urihttp://hdl.handle.net/11693/77128
dc.language.isoEnglishen_US
dc.publisherAmerican Physiological Societyen_US
dc.relation.isversionof10.1152/ajprenal.00097.2021en_US
dc.source.titleAmerican Journal of Physiology: Renal Physiologyen_US
dc.subjectChildrenen_US
dc.subjectExtracellular vesiclesen_US
dc.subjectNephrotic syndromeen_US
dc.subjectPhospho-p38en_US
dc.subjectRAC1en_US
dc.titleCirculating extracellular vesicles of patients with steroid-sensitive nephrotic syndrome have higher RAC1 and induce recapitulation of nephrotic syndrome phenotype in podocytesen_US
dc.typeArticleen_US

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