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Pediatric Nephrology

, Volume 34, Issue 3, pp 379–388 | Cite as

Shiga toxin triggers endothelial and podocyte injury: the role of complement activation

  • Carlamaria ZojaEmail author
  • Simona Buelli
  • Marina Morigi
Review

Abstract

Shiga toxin (Stx)-producing Escherichia coli (STEC) is the offending agent in post-diarrhea-associated hemolytic uremic syndrome (HUS), a disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney failure, with thrombi occluding the renal microvasculature. Endothelial dysfunction has been recognized as the trigger event in the development of microangiopathic processes. Glomerular endothelial cells are susceptible to the toxic effects of Stxs that, via nuclear factor kappa B (NF-κB) activation, induce the expression of genes encoding for adhesion molecules and chemokines, culminating in leukocyte adhesion and platelet thrombus formation on the activated endothelium. Complement activation via the alternative pathway has been seen in patients during the acute phase of STEC-associated HUS. Experimental evidence has highlighted the role of complement proteins in driving glomerular endothelium toward a thrombogenic phenotype. At the glomerular level, podocytes are also an important target of Stx-induced complement activation. Glomerular injury as a consequence of podocyte dysfunction and loss is thus a mechanism that might affect long-term renal outcomes in the disease. New approaches to targeting the complement system may be useful therapeutic options for patients with STEC-HUS.

Keywords

Shiga toxin Enterohemorrhagic Escherichia coli Hemolytic uremic syndrome Endothelial injury Microvascular thrombosis Podocytes Complement alternative pathway 

Notes

Acknowledgements

The authors thank Professor Giuseppe Remuzzi for reviewing the manuscript and Dr. Antonella Piccinelli for helping in figure preparation. Dr. Kerstin Mierke and Manuela Passera helped with preparing the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© IPNA 2017

Authors and Affiliations

  1. 1.Centro Anna Maria Astori, Science and Technology Park Kilometro RossoIRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”BergamoItaly

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