Artículo
Eliglustat prevents Shiga toxin 2 cytotoxic effects in human renal tubular epithelial cells
Sanchez, Daiana Soledad
; Fischer Sigel, Lilian Karina
; Balestracci, Alejandro; Ibarra, Cristina Adriana
; Amaral, María Marta
; Silberstein, Claudia Marcela
Fecha de publicación:
04/2022
Editorial:
International Pediatric Research Foundation
Revista:
Pediatric Research
ISSN:
0031-3998
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Background: Shiga toxin-producing Escherichia coli is responsible for post-diarrheal (D+) hemolytic uremic syndrome (HUS), which is a cause of acute renal failure in children. The glycolipid globotriaosylceramide (Gb3) is the main receptor for Shiga toxin (Stx) in kidney target cells. Eliglustat (EG) is a specific and potent inhibitor of glucosylceramide synthase, first step of glycosphingolipid biosynthesis, actually used for the treatment of Gaucher’s disease. The aim of the present work was to evaluate the efficiency of EG in preventing the damage caused by Stx2 in human renal epithelial cells. Methods: Human renal tubular epithelial cell (HRTEC) primary cultures were pre-treated with different dilutions of EG followed by co-incubation with EG and Stx2 at different times, and cell viability, proliferation, apoptosis, tubulogenesis, and Gb3 expression were assessed. Results: In HRTEC, pre-treatments with 50 nmol/L EG for 24 h, or 500 nmol/L EG for 6 h, reduced Gb3 expression and totally prevented the effects of Stx2 on cell viability, proliferation, and apoptosis. EG treatment also allowed the development of tubulogenesis in 3D-HRTEC exposed to Stx2. Conclusions: EG could be a potential therapeutic drug for the prevention of acute kidney injury caused by Stx2. Impact: For the first time, we have demonstrated that Eliglustat prevents Shiga toxin 2 cytotoxic effects on human renal epithelia, by reducing the expression of the toxin receptor globotriaosylceramide.The present work also shows that Eliglustat prevents Shiga toxin 2 effects on tubulogenesis of renal epithelial cells.Eliglustat, actually used for the treatment of patients with Gaucher’s disease, could be a therapeutic strategy to prevent the renal damage caused by Shiga toxin.
Palabras clave:
NEPHROLOGY
,
INFECTIOUS DISEASE
,
ACUTE KIDNEY INJURY
,
SHIGA TOXIN 2
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IFIBIO HOUSSAY)
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Citación
Sanchez, Daiana Soledad; Fischer Sigel, Lilian Karina; Balestracci, Alejandro; Ibarra, Cristina Adriana; Amaral, María Marta; et al.; Eliglustat prevents Shiga toxin 2 cytotoxic effects in human renal tubular epithelial cells; International Pediatric Research Foundation; Pediatric Research; 91; 5; 4-2022; 1121-1129
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