SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells

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dc.contributor.authorSilva-Aguiar, Rodrigo P.
dc.contributor.authorTeixeira, Douglas E.
dc.contributor.authorPeruchetti, Diogo B.
dc.contributor.authorFlorentino, Lucas S.
dc.contributor.authorPeres, Rodrigo A. S.
dc.contributor.authorGomes, Carlos P.
dc.contributor.authorMarzolo, Maria-Paz
dc.contributor.authorRocco, Patricia M. R.
dc.contributor.authorPinheiro, Ana Acacia S.
dc.contributor.authorCaruso-Neves, Celso
dc.date.accessioned2025-01-20T21:02:55Z
dc.date.available2025-01-20T21:02:55Z
dc.date.issued2022
dc.description.abstractPatients with COVID-19 have high prevalence of albuminuria which is used as a marker of progression of renal disease and is associated with severe COVID-19. We hypothesized that SARS-CoV-2 spike protein (S protein) could modulate albumin handling in proximal tubule epithelial cells (PTECs) and, consequently contribute to the albuminuria observed in patients with COVID-19. In this context, the possible effect of S protein on albumin endocytosis in PTECs was investigated. Two PTEC lines were used: HEK-293A and LLC-PK1. Incubation of both cell types with S protein for 16 h inhibited albumin uptake at the same magnitude. This effect was associated with canonical megalin-mediated albumin endocytosis because: (1) DQ-albumin uptake, a marker of the lyso-somal degradation pathway, was reduced at a similar level compared with fluorescein isothiocyanate (FITC)-albumin uptake; (2) dextran-FITC uptake, a marker of fluid-phase endocytosis, was not changed; (3) cell viability and proliferation were not changed. The inhibitory effect of S protein on albumin uptake was only observed when it was added at the luminal membrane, and it did not involve the ACE2/Ang II/AT1R axis. Although both cells uptake S protein, it does not seem to be required for modulation of albumin endocytosis. The mechanism underlying the inhibition of albumin uptake by S protein encompasses a decrease in megalin expression without changes in megalin trafficking and stability. These results reveal a possible mechanism to explain the albu-minuria observed in patients with COVID-19.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bbadis.2022.166496
dc.identifier.eissn1879-260X
dc.identifier.issn0925-4439
dc.identifier.urihttps://doi.org/10.1016/j.bbadis.2022.166496
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93101
dc.identifier.wosidWOS:000842750100001
dc.issue.numero12
dc.language.isoen
dc.revistaBiochimica et biophysica acta-molecular basis of disease
dc.rightsacceso restringido
dc.subjectProximal tubule
dc.subjectAlbumin endocytosis
dc.subjectSpike protein
dc.subjectSARS-CoV-2
dc.subjectMegalin
dc.subjectCOVID-19
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleSARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells
dc.typeartículo
dc.volumen1868
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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