Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia.
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.


METHODS
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.
Garovic
Vesna D
VD
Division of Nephrology and Hypertension Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. garovic.vesna@mayo.edu
Wagner
Steven J
SJ
Petrovic
Lydia M
LM
Gray
Catherine E
CE
Hall
Pauline
P
Sugimoto
Hikaru
H
Kalluri
Raghu
R
Grande
Joseph P
JP
D000293:Adolescent; D000328:Adult; D000818:Animals; D000906:Antibodies / Q000009:adverse effects; D001706:Biopsy; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1
D000906:Antibodies; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; C503967:SYNPO protein, human; C503968:Synpo protein, mouse; D042461:Vascular Endothelial Growth Factor A; C113267:nephrin; D040281:Vascular Endothelial Growth Factor Receptor-1