Surface megalin expression is a target to the inhibitory effect of bradykinin on the renal albumin endocytosis

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dc.contributor.authorAlves, Sarah A. S.
dc.contributor.authorFlorentino, Lucas S.
dc.contributor.authorTeixeira, Douglas E.
dc.contributor.authorSilva-Aguiar, Rodrigo P.
dc.contributor.authorPeruchetti, Diogo B.
dc.contributor.authorOliveira, Ana Carolina
dc.contributor.authorScharfstein, Julio
dc.contributor.authorMarzolo, Maria-Paz
dc.contributor.authorPinheiro, Ana Acacia S.
dc.contributor.authorCaruso-Neves, Celso
dc.date.accessioned2025-01-20T22:07:49Z
dc.date.available2025-01-20T22:07:49Z
dc.date.issued2021
dc.description.abstractMegalin-mediated albumin endocytosis plays a critical role in albumin reabsorption in proximal tubule (PT) epithelial cells (PTECs). Some studies have pointed out the modulatory effect of bradykinin (BK) on urinary protein excretion, but its role in PT protein endocytosis has not yet been determined. Here, we studied the possible correlation between BK and albumin endocytosis in PT. Using LLC-PK1 cells, a model of PTECs, we showed that BK specifically inhibited megalin-mediated albumin endocytosis. This inhibitory effect of BK was mediated by B2 receptor (B2R) because it was abolished by HOE140, an antagonist of B2R, but it was not affected by Lys-des-Arg(9)-BK, an antagonist of B1. BK induced the stall of megalin in EEA1(+) endosomes, but not in LAMP1(+) lysosomes, leading to a decrease in surface megalin expression. In addition, we showed that BK, through B2R, activated calphostin C-sensitive protein kinase C, which mediated its effect on the surface megalin expression and albumin endocytosis. These results reveal an important modulatory mechanism of PT albumin endocytosis by BK, which opens new possibilities to understanding the effect of BK on urinary albumin excretion.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.peptides.2021.170646
dc.identifier.eissn1873-5169
dc.identifier.issn0196-9781
dc.identifier.urihttps://doi.org/10.1016/j.peptides.2021.170646
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94261
dc.identifier.wosidWOS:000701722200006
dc.language.isoen
dc.revistaPeptides
dc.rightsacceso restringido
dc.subjectG protein-coupled receptor
dc.subjectProtein kinase C
dc.subjectEndocytosis
dc.subjectKidney
dc.subjectBradykinin
dc.subjectAlbuminuria
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleSurface megalin expression is a target to the inhibitory effect of bradykinin on the renal albumin endocytosis
dc.typeartículo
dc.volumen146
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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