Semaphorin3a disrupts podocyte foot processes causing acute proteinuria

R. Tapia, Fangxia Guan, I. Gershin, J. Teichman, G. Villegas, A. Tufro

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Semaphorin3a was discovered as a secreted guidance protein that acts as a chemorepellent to migrating axons and endothelial cells. In the adult mouse kidney, it is expressed in podocytes and collecting tubules. Here, we show that exogenous semaphorin3a caused acute nephrotic range proteinuria associated with podocyte foot process effacement and fusion, endothelial cell damage, decreased vascular endothelial growth factor-A receptor expression, and downregulation of the slit-diaphragm proteins podocin, nephrin, and CD2-associated protein. When vascular endothelial growth factor 165 was administered at the same time as Semaphorin3a, no proteinuria or renal ultrastructural abnormalities occurred, suggesting that semaphorin3a effects may be mediated, in part, by downregulation of vascular endothelial growth factor receptor 2 signaling. Our findings indicate that a balance of semaphorin3a to vascular endothelial growth factor-A may be important for glomerular filtration barrier homeostasis.

Original languageEnglish (US)
Pages (from-to)733-740
Number of pages8
JournalKidney International
Volume73
Issue number6
DOIs
StatePublished - Mar 2008

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Podocytes
Proteinuria
Vascular Endothelial Growth Factor A
Down-Regulation
Glomerular Filtration Barrier
Endothelial Cells
Kidney
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor
Diaphragm
Axons
Proteins
Homeostasis
nephrin
CD2-associated protein
NPHS2 protein
human VEGFA protein

Keywords

  • Podocyte effacement
  • Proteinuria
  • Semaphorin3a
  • VEGF-A
  • VEGFR2

ASJC Scopus subject areas

  • Nephrology

Cite this

Tapia, R., Guan, F., Gershin, I., Teichman, J., Villegas, G., & Tufro, A. (2008). Semaphorin3a disrupts podocyte foot processes causing acute proteinuria. Kidney International, 73(6), 733-740. https://doi.org/10.1038/sj.ki.5002726

Semaphorin3a disrupts podocyte foot processes causing acute proteinuria. / Tapia, R.; Guan, Fangxia; Gershin, I.; Teichman, J.; Villegas, G.; Tufro, A.

In: Kidney International, Vol. 73, No. 6, 03.2008, p. 733-740.

Research output: Contribution to journalArticle

Tapia, R, Guan, F, Gershin, I, Teichman, J, Villegas, G & Tufro, A 2008, 'Semaphorin3a disrupts podocyte foot processes causing acute proteinuria', Kidney International, vol. 73, no. 6, pp. 733-740. https://doi.org/10.1038/sj.ki.5002726
Tapia, R. ; Guan, Fangxia ; Gershin, I. ; Teichman, J. ; Villegas, G. ; Tufro, A. / Semaphorin3a disrupts podocyte foot processes causing acute proteinuria. In: Kidney International. 2008 ; Vol. 73, No. 6. pp. 733-740.
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