ArticleJournal of the American Society of Nephrology : JASN2014
Shiga toxin promotes podocyte injury in experimental hemolytic uremic syndrome via activation of the alternative pathway of complement.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Eculizumab in Shiga toxin-producing Escherichia coli hemolytic uremic syndrome: a systematic review.Pediatric nephrology (Berlin, Germany) · 2024Pooled it
- Molecular determinants of STEC-HUS: from complement activation to microvascular thrombosis.Frontiers in immunology · 2026Article
- The Role of the Complement System in the Pathogenesis of Infectious Forms of Hemolytic Uremic Syndrome.Biomolecules · 2023Review
- Predictive prognostic value of glomerular C3 deposition in IgA nephropathy.Journal of nephrology · 2023Article
- Article
- The Shiga Toxin Receptor Globotriaosylceramide as Therapeutic Target in Shiga ToxinMicroorganisms · 2021Article
- Sustained activation of C3aR in a human podocyte line impairs the morphological maturation of the cells.Molecular medicine reports · 2020Article
- Treatment-resistant nephrotic syndrome in dense deposit disease: complement-mediated glomerular capillary wall injury?Pediatric nephrology (Berlin, Germany) · 2020Article
- Article
- Eculizumab in the treatment of Shiga toxin haemolytic uraemic syndrome.Pediatric nephrology (Berlin, Germany) · 2019Review
- Effect of Timing and Complement Receptor Antagonism on Intragraft Recruitment and Protolerogenic Effects of Mesenchymal Stromal Cells in Murine Kidney Transplantation.Transplantation · 2019Article
- Roles of Shiga Toxins in Immunopathology.Toxins · 2019Review
- Shiga toxin triggers endothelial and podocyte injury: the role of complement activation.Pediatric nephrology (Berlin, Germany) · 2019Review
- Complement Activation Contributes to the Pathophysiology of Shiga Toxin-Associated Hemolytic Uremic Syndrome.Microorganisms · 2019Review
- Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic uremic syndrome (HUS).Pediatric nephrology (Berlin, Germany) · 2018Review
- The MFHR1 Fusion Protein Is a Novel Synthetic Multitarget Complement Inhibitor with Therapeutic Potential.Journal of the American Society of Nephrology : JASN · 2018Article
- Modeling Hemolytic-Uremic Syndrome: In-Depth Characterization of Distinct Murine Models Reflecting Different Features of Human Disease.Frontiers in immunology · 2018Article
- Review
- Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea.Clinical kidney journal · 2017Article
- Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome.Journal of innate immunity · 2017Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Shiga toxin (Stx)-producing Escherichia coli is the offending agent of postdiarrhea-associated hemolytic uremic syndrome (HUS), a disorder of glomerular ischemic damage and widespread microvascular thrombosis. We previously documented that Stx induces glomerular complement activation, generating C3a responsible for microvascular thrombosis in experimental HUS. Here, we show that the presence of C3 deposits on podocytes is associated with podocyte damage and loss in HUS mice generated by the coinjection of Stx2 and LPS. Because podocyte adhesion to the glomerular basement membrane is mediated by integrins, the relevance of integrin-linked kinase (ILK) signals in podocyte dysfunction was evaluated. Podocyte expression of ILK increased after the injection of Stx2/LPS and preceded the upregulation of Snail and downregulation of nephrin and α-actinin-4. Factor B deficiency or pretreatment with an inhibitory antibody to factor B protected mice against Stx2/LPS-induced podocyte dysregulation. Similarly, pretreatment with a C3a receptor antagonist limited podocyte loss and changes in ILK, Snail, and α-actinin-4 expression. In cultured podocytes, treatment with C3a reduced α-actinin-4 expression and promoted ILK-dependent nuclear expression of Snail and cell motility. These results suggest that Stx-induced activation of the alternative pathway of complement and generation of C3a promotes ILK signaling, leading to podocyte dysfunction and loss in Stx-HUS.
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