Decreased Nephrin and GLEPP-1, but Increased VEGF, Flt-1, and Nitrotyrosine, Expressions in Kidney Tissue Sections From Women With Preeclampsia

Reprod Sci. 2009 Oct;16(10):970-9. doi: 10.1177/1933719109338630. Epub 2009 Jun 15.

Abstract

Renal injury is a common pathophysiological feature in women with preeclampsia as evidenced by increased protein leakage (proteinuria) and glomerular injury (glomerular endotheliosis). Recently, podocyturia was found in preeclampsia, suggesting podocyte shedding occurs in this pregnancy disorder. However, podocyte function in preeclampsia is poorly understood. In this study, the authors have examined podocyte-specific protein expressions for nephrin, glomerular epithelial protein 1 (GLEPP-1), and ezrin in kidney biopsy tissue sections from women with preeclampsia. Expressions for vascular endothelial growth factor (VEGF) and its receptor Flt-1 and oxidative stress marker nitrotyrosine and antioxidant CuZn-superoxide dismutase (CuZn-SOD) were also examined. Kidney tissue sections from nonhypertensive and chronic hypertensive participants were stained as controls. The findings were (1) nephrin and GLEPP-1 were mainly expressed in glomerular podocytes; (2) ezrin was expressed in both glomerular podocytes and tubular epithelial cells; (3) compared to tissue sections from nonhypertensive and chronic hypertensive participants, nephrin and GLEPP-1 expressions were much reduced in tissue sections from preeclampsia and ezrin expression was reduced in podocytes; (4) enhanced VEGF, Flt-1, and nitrotyrosine, but reduced CuZn-SOD, expressions were observed in both glomerular podocytes and endothelial cells in tissue sections from preeclampsia; and (5) the expression pattern for nephrin, GLEPP-1, ezrin, VEGF, Flt-1, and CuZn-SOD were similar between tissue sections from nonhypertensive and chronic hypertensive participants. Although the authors could not conclude from this biopsy study whether the podocyte injury is the cause or effect of the preeclampsia phenotype, the data provide compelling evidence that podocyte injury accompanied by altered angiogenesis process and increased oxidative stress occurs in kidney of patients with preeclampsia.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Female
  • Gene Expression
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Membrane Proteins / biosynthesis*
  • Podocytes / metabolism
  • Podocytes / pathology
  • Pre-Eclampsia / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / biosynthesis*
  • Retrospective Studies
  • Tyrosine / analogs & derivatives*
  • Tyrosine / biosynthesis
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis*

Substances

  • Membrane Proteins
  • Vascular Endothelial Growth Factor A
  • nephrin
  • 3-nitrotyrosine
  • Tyrosine
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • PTPRO protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3