Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/ijms22115615
Keywords
hemolytic uremic syndrome; STEC-HUS; Shiga toxin; human glomerular microvascular endothelial cells from pediatric and adult origin
Funding
- Principal Clinician Grant, Radboudumc, Nijmegen, the Netherlands
- Canadian Institutes of Health Research [376777]
- SickKids intramural grants
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Hemolytic uremic syndrome (HUS) is a disease characterized by a triad of symptoms caused by infection with Shiga toxin-producing Escherichia coli bacteria. While predominantly affecting children, the syndrome leads to kidney damage. Research has shown that cells isolated from pediatric and adult kidneys do not significantly differ in their biological responses to Shiga toxin.
Hemolytic uremic syndrome (HUS) is characterized by a triad of symptoms consisting of hemolytic anemia, thrombocytopenia and acute renal failure. The most common form of HUS is caused by an infection with Shiga toxin (Stx) producing Escherichia coli bacteria (STEC-HUS), and the kidneys are the major organs affected. The development of HUS after an infection with Stx occurs most frequently in children under the age of 5 years. However, the cause for the higher incidence of STEC-HUS in children compared to adults is still not well understood. Human glomerular microvascular endothelial cells (HGMVECs) isolated and cultured from pediatric and adult kidney tissue were investigated with respect to Stx binding and different cellular responses. Shiga toxin-1 (Stx-1) inhibited protein synthesis in both pediatric and adult HGMVECs in a dose-dependent manner at basal conditions. The preincubation of pediatric and adult HGMVECs for 24 hrs with TNF alpha resulted in increased Stx binding to the cell surface and a 20-40% increase in protein synthesis inhibition in both age groups. A decreased proliferation of cells was found when a bromodeoxyuridine (BrdU) assay was performed. A trend towards a delay in endothelial wound closure was visible when pediatric and adult HGMVECs were incubated with Stx-1. Although minor differences between pediatric HGMVECs and adult HGMVECs were found in the assays applied in this study, no significant differences were observed. In conclusion, we have demonstrated that in vitro primary HGMVECs isolated from pediatric and adult kidneys do not significantly differ in their cell biological responses to Stx-1.
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