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10.1016/j.bbadis.2022.166496

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suck abstract from ncbi


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pmid35863591      Biochim+Biophys+Acta+Mol+Basis+Dis 2022 ; 1868 (12): 166496
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  • SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells #MMPMID35863591
  • Silva-Aguiar RP; Teixeira DE; Peruchetti DB; Florentino LS; Peres RAS; Gomes CP; Marzolo MP; Rocco PMR; Pinheiro AAS; Caruso-Neves C
  • Biochim Biophys Acta Mol Basis Dis 2022[Dec]; 1868 (12): 166496 PMID35863591show ga
  • Patients 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 lysosomal 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 albuminuria observed in patients with COVID-19.
  • |*COVID-19[MESH]
  • |*Low Density Lipoprotein Receptor-Related Protein-2/metabolism[MESH]
  • |Albumins/metabolism/pharmacology[MESH]
  • |Albuminuria/metabolism[MESH]
  • |Angiotensin-Converting Enzyme 2[MESH]
  • |Cells, Cultured[MESH]
  • |Dextrans/pharmacology[MESH]
  • |Endocytosis/physiology[MESH]
  • |Epithelial Cells/metabolism[MESH]
  • |Fluorescein-5-isothiocyanate/metabolism/pharmacology[MESH]
  • |Humans[MESH]
  • |SARS-CoV-2[MESH]


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