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Volume 12
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Article

Shiga Toxin Selectively Upregulates Expression of Syndecan-4 and Adhesion Molecule ICAM-1 in Human Glomerular Microvascular Endothelium

by
Elena B. Volokhina
1,2,*,
Wouter J. C. Feitz
1,
Lonneke M. Elders
1,
Thea J. A. M. van der Velden
1,
Nicole C. A. J. van de Kar
1 and
Lambertus P. W. J. van den Heuvel
1,2,3
1
Department of Pediatric Nephrology, Amalia Children’s Hospital, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
2
Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
3
Department of Pediatrics, University Hospitals Leuven, 3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(7), 435; https://doi.org/10.3390/toxins12070435
Submission received: 5 June 2020 / Revised: 23 June 2020 / Accepted: 29 June 2020 / Published: 3 July 2020
(This article belongs to the Special Issue Pathogenesis of Hemolytic Uremic Syndrome Caused by Shiga Toxin-Producing Escherichia coli Infections)
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Abstract

Hemolytic uremic syndrome (HUS) is a severe renal disease that is often preceded by infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). The exact mechanism of Stx-mediated inflammation on human glomerular microvascular endothelial cells (HGMVECs) during HUS is still not well understood. In this study, we investigated the effect of Stx1 on the gene expression of proteins involved in leucocyte-mediated and complement-mediated inflammation. Our results showed that Stx1 enhances the mRNA and protein expression of heparan sulfate proteoglycan (HSPG) syndecan-4 in HGMVECs pre-stimulated with tumor necrosis factor α (TNFα). CD44 was upregulated on mRNA but not on protein level; no effect on the mRNA expression of other tested HSPGs glypican-1 and betaglycan was observed. Furthermore, Stx1 upregulated the mRNA, cell surface expression, and supernatant levels of the intercellular adhesion molecule-1 (ICAM-1) in HGMVECs. Interestingly, no effect on the protein levels of alternative pathway (AP) components was observed, although C3 mRNA was upregulated. All observed effects were much stronger in HGMVECs than in human umbilical endothelial cells (HUVECs), a common model cell type used in endothelial studies. Our results provide new insights into the role of Stx1 in the pathogenesis of HUS. Possibilities to target the overexpression of syndecan-4 and ICAM-1 for STEC-HUS therapy should be investigated in future studies.
Keywords: hemolytic uremic syndrome; human glomerular microvascular endothelium; Shiga toxin 1; gene expression; heparan sulfate proteoglycans; syndecan-4; ICAM-1 hemolytic uremic syndrome; human glomerular microvascular endothelium; Shiga toxin 1; gene expression; heparan sulfate proteoglycans; syndecan-4; ICAM-1

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MDPI and ACS Style

Volokhina, E.B.; Feitz, W.J.C.; Elders, L.M.; van der Velden, T.J.A.M.; van de Kar, N.C.A.J.; van den Heuvel, L.P.W.J. Shiga Toxin Selectively Upregulates Expression of Syndecan-4 and Adhesion Molecule ICAM-1 in Human Glomerular Microvascular Endothelium. Toxins 2020, 12, 435. https://doi.org/10.3390/toxins12070435

AMA Style

Volokhina EB, Feitz WJC, Elders LM, van der Velden TJAM, van de Kar NCAJ, van den Heuvel LPWJ. Shiga Toxin Selectively Upregulates Expression of Syndecan-4 and Adhesion Molecule ICAM-1 in Human Glomerular Microvascular Endothelium. Toxins. 2020; 12(7):435. https://doi.org/10.3390/toxins12070435

Chicago/Turabian Style

Volokhina, Elena B., Wouter J. C. Feitz, Lonneke M. Elders, Thea J. A. M. van der Velden, Nicole C. A. J. van de Kar, and Lambertus P. W. J. van den Heuvel. 2020. "Shiga Toxin Selectively Upregulates Expression of Syndecan-4 and Adhesion Molecule ICAM-1 in Human Glomerular Microvascular Endothelium" Toxins 12, no. 7: 435. https://doi.org/10.3390/toxins12070435

APA Style

Volokhina, E. B., Feitz, W. J. C., Elders, L. M., van der Velden, T. J. A. M., van de Kar, N. C. A. J., & van den Heuvel, L. P. W. J. (2020). Shiga Toxin Selectively Upregulates Expression of Syndecan-4 and Adhesion Molecule ICAM-1 in Human Glomerular Microvascular Endothelium. Toxins, 12(7), 435. https://doi.org/10.3390/toxins12070435

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