biostudies-literatureBowen EEKidney Research UKMedical Research CouncilNational Institute for Health Research (NIHR)761-777.e8https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617617biostudies-literatureUnknown4(11)<h4>Background</h4>Shiga toxin (Stx)-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the leading cause of acute kidney injury in children, with an associated mortality of up to 5%. The mechanisms underlying STEC-HUS and why the glomerular microvasculature is so susceptible to injury following systemic Stx infection are unclear.<h4>Methods</h4>Transgenic mice were engineered to express the Stx receptor (Gb3) exclusively in their kidney podocytes (Pod-Gb3) and challenged with systemic Stx. Human glomerular cell models and kidney biopsies from patients with STEC-HUS were also studied.<h4>Findings</h4>Stx-challenged Pod-Gb3 mice developed STEC-HUS. This was mediated by a reduction in podocyte vascular endothelial growth factor A (VEGF-A), which led to loss of glomerular endoMed (New York, N.Y.)Shiga toxin targets the podocyte causing hemolytic uremic syndrome through endothelial complement activation.PMC7617617MR/K010492/1MR/T002263/1MR/W019582/1G0501901G0800200MR/W024187/1SP/FSGS1/2013CL-2018-25-002ACF-2012-25-005IN_004_20190305INT_002_20220705ST_008_20181123MR/M018237/1G0901987TF_007_20151127RP42/2012Lay ACMorgan BPDiatlov DSatchell SCWells SBohorquez-Hernandez AButler MJWherlock MDStewart MLarkai EMSRostam-Shirazi NMoppett JCoward RJMHurcombe JAPope RJPWelsh GITeboul LKeir LSFarmer LKWalker PDBarrington FBruno VSaleem MAOrtiz-Sandoval CGBowen EELicht CfalseShiga toxin targets the podocyte causing hemolytic uremic syndrome through endothelial complement activation.<h4>Background</h4>Shiga toxin (Stx)-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the leading cause of acute kidney injury in children, with an associated mortality of up to 5%. The mechanisms underlying STEC-HUS and why the glomerular microvasculature is so susceptible to injury following systemic Stx infection are unclear.<h4>Methods</h4>Transgenic mice were engineered to express the Stx receptor (Gb3) exclusively in their kidney podocytes (Pod-Gb3) and challenged with systemic Stx. Human glomerular cell models and kidney biopsies from patients with STEC-HUS were also studied.<h4>Findings</h4>Stx-challenged Pod-Gb3 mice developed STEC-HUS. This was mediated by a reduction in podocyte vascular endothelial growth factor A (VEGF-A), which led to loss of glomerular endo2023-01-01T00:00:00Z2023 Nov2026-06-02T17:34:18.115Z2025-07-12T03:04:36.257ZS-EPMC76176173786305810.1016/j.medj.2023.09.002