ArticleThe Journal of clinical investigation2012
The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 95 citations in OpenAlex.
- Modeling Shiga toxin-induced human renal-specific microvascular injury.Integrative biology : quantitative biosciences from nano to macro · 2024Article
- Chemokines, molecular drivers of thromboinflammation and immunothrombosis.Frontiers in immunology · 2023Review
- Hemolytic Uremic Syndrome in Children.Turkish archives of pediatrics · 2021Article
- Unraveling the epigenetic landscape of glomerular cells in kidney disease.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Review
- RAB5A and TRAPPC6B are novel targets for Shiga toxin 2a inactivation in kidney epithelial cells.Scientific reports · 2020Article
- Review
- Tissue Responses to Shiga Toxin in Human Intestinal Organoids.Cellular and molecular gastroenterology and hepatology · 2020Article
- Shiga toxin triggers endothelial and podocyte injury: the role of complement activation.Pediatric nephrology (Berlin, Germany) · 2019Review
- Endothelium structure and function in kidney health and disease.Nature reviews. Nephrology · 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
- Clinical and Laboratory Predictors of Shiga Toxin-Producing Escherichia coli Infection in Children With Bloody Diarrhea.Journal of the Pediatric Infectious Diseases Society · 2018Article
- Modeling Hemolytic-Uremic Syndrome: In-Depth Characterization of Distinct Murine Models Reflecting Different Features of Human Disease.Frontiers in immunology · 2018Article
- Shiga Toxin Therapeutics: Beyond Neutralization.Toxins · 2017Review
- Human mannose-binding lectin inhibitor prevents Shiga toxin-induced renal injury.Kidney international · 2016Article
- A Stromal Cell-Derived Factor 1α Analogue Improves Endothelial Cell Function in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome.Molecular medicine (Cambridge, Mass.) · 2016Article
- Shiga Toxin Mediated Neurologic Changes in Murine Model of Disease.Frontiers in cellular and infection microbiology · 2016Article
- Crosstalk in glomerular injury and repair.Current opinion in nephrology and hypertension · 2015Review
- A novel mechanism of bacterial toxin transfer within host blood cell-derived microvesicles.PLoS pathogens · 2015Article
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced changes in gene expression and their contribution to the pathogenesis of HUS. Stx function by inactivating host ribosomes but can also alter gene expression at concentrations that minimally affect global protein synthesis. Gene expression profiling of human microvascular endothelium treated with Stx implicated a role for activation of CXCR4 and CXCR7 by their shared cognate chemokine ligand (stromal cell-derived factor-1 [SDF-1]) in Stx-mediated pathophysiology. The changes in gene expression required a catalytically active Stx A subunit and were mediated by enhanced transcription and mRNA stability. Stx also enhanced the association of CXCR4, CXCR7, and SDF1 mRNAs with ribosomes. In a mouse model of Stx-mediated pathology, we noted changes in plasma and tissue content of CXCR4, CXCR7, and SDF-1 after Stx exposure. Furthermore, inhibition of the CXCR4/SDF-1 interaction decreased endothelial activation and organ injury and improved animal survival. Finally, in children infected with E. coli O157:H7, plasma SDF-1 levels were elevated in individuals who progressed to HUS. Collectively, these data implicate the CXCR4/CXCR7/SDF-1 pathway in Stx-mediated pathogenesis and suggest novel therapeutic strategies for prevention and/or treatment of complications associated with E. coli O157:H7 infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.