NDT Advance Access originally published online on January 25, 2007
Nephrology Dialysis Transplantation 2007 22(4):1136-1143; doi:10.1093/ndt/gfl711
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Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia
1Division of Nephrology and Hypertension, Mayo Medical College, Rochester, MN, USA, 2Department of Pathology, New York University, New York, NY, USA, 3Department of Pathology, University of Cape Town, South Africa and 4Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Correspondence and offprint requests to: Vesna D. Garovic, Division of Nephrology and Hypertension Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA. Email: garovic.vesna{at}mayo.edu
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Abstract |
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Background. Preeclampsia is a pregnancy-specific disorder characterized by hypertension and proteinuria. In other disease states, proteinuria has been linked to altered expressions of podocyte foot-process proteins, but this has not been studied in women with preeclampsia. We sought to test the hypothesis that proteinuria in preeclampsia is associated with dysregulated expression of the podocyte cytoskeleton and/or tight junction proteins.
Mathods. Renal tissue was obtained from autopsy material from seven women who had severe preeclampsia during the second half of their pregnancies up to 48 h after delivery, and who subsequently died. As controls, we used autopsy material from two women who died accidentally during the second half of their otherwise normal pregnancies. Immunohistochemical stains for nephrin, synaptopodin and podocin were performed on representative sections prepared from paraffin-embedded material.
Results. Expression of both nephrin and synaptopodin was markedly decreased in preeclamptic compared with control kidney sections. By contrast, both cases and controls demonstrated strong staining for podocin.
Conclusions. We conclude that down-regulation of nephrin and synaptopodin is associated with proteinuria in women with preeclampsia. Recent studies have demonstrated that soluble vascular endothelial growth factor receptor 1 (sFlt-1) levels are elevated in preeclampsia compared with normal pregnancy. Studies in mice have shown that sFlt-1 may play a role in inducing proteinuria by neutralizing vascular endothelial growth factor (VEGF) and suppressing nephrin. Proteinuria and elevations of sFlt-1 in preeclampsia are temporally related, further supporting a possible role of sFlt-1 in the dysregulation of podocyte foot-process proteins.
Keywords: nephrin; parietal epithelial cell; podocin; preeclampsia; proteinuria; slit diaphragm; synaptopodin
Received for publication: 8. 3.06
Accepted in revised form: 2.11.06
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