A study of VEGF and its receptors in two rat models of proteinuria

John Kanellis, Vicki Levidiotis, Tiffany Tee Fern Khong, Alison J Cox, Steven A Stacker, Richard E Gilbert, Mark E Cooper, David A Power

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND: The high level of expression of vascular endothelial growth factor (VEGF) in normal podocyte foot processes suggests that VEGF has an important role in maintaining normal glomerular function. While altered VEGF expression occurs in many glomerular diseases, a direct role for VEGF in the pathogenesis of proteinuria has not been demonstrated. METHODS: Expression of VEGF and its receptors (VEGFR-1 and VEGFR-2) was examined in passive Heymann nephritis (PHN) and puromycin aminonucleoside nephrosis (PAN), by immunohistochemistry, in situ hybridization, Northern and Western blotting. Inhibition of VEGF in the PAN model was performed by administration of a blocking antibody. RESULTS: In both models, glomeruli showed upregulation of VEGF and VEGF receptors compared to control animals. VEGF mRNA was increased most significantly (5-fold) at day 5 after induction of PHN, prior to the onset of proteinuria, with persistent upregulation (3-fold) at day 21. Increased VEGF mRNA was also seen in PAN, but it was less marked. In situ hybridization and immunohistochemistry localized VEGF predominantly to podocytes. Increased expression of VEGFR-1 and VEGFR-2 protein was seen in glomerular endothelial cells of PHN and PAN rats by immunohistochemistry, as was VEGFR-2 mRNA by in situ hybridization. Upregulation of VEGFR-1 by endothelial cells was more striking in the PAN model than PHN. Administration of a blocking antibody to rats with PAN did not affect proteinuria, creatinine clearance or sodium excretion. CONCLUSION: The expression of VEGF and its receptors is significantly increased in the PHN and PAN rat models of proteinuria suggesting a role for VEGF in the disease process. VEGF may have an important role in promoting glomerular repair in a variety of glomerular diseases. Copyright 2004 S. Karger AG, Basel
Original languageEnglish
Pages (from-to)26 - 36
Number of pages11
JournalNephron Physiology
Volume96
Issue number1
DOIs
Publication statusPublished - 2004
Externally publishedYes

Cite this

Kanellis, J., Levidiotis, V., Khong, T. T. F., Cox, A. J., Stacker, S. A., Gilbert, R. E., ... Power, D. A. (2004). A study of VEGF and its receptors in two rat models of proteinuria. Nephron Physiology, 96(1), 26 - 36. https://doi.org/10.1159/000075577
Kanellis, John ; Levidiotis, Vicki ; Khong, Tiffany Tee Fern ; Cox, Alison J ; Stacker, Steven A ; Gilbert, Richard E ; Cooper, Mark E ; Power, David A. / A study of VEGF and its receptors in two rat models of proteinuria. In: Nephron Physiology. 2004 ; Vol. 96, No. 1. pp. 26 - 36.
@article{e3ee4b75de2949f087ec4e917c08b42b,
title = "A study of VEGF and its receptors in two rat models of proteinuria",
abstract = "BACKGROUND: The high level of expression of vascular endothelial growth factor (VEGF) in normal podocyte foot processes suggests that VEGF has an important role in maintaining normal glomerular function. While altered VEGF expression occurs in many glomerular diseases, a direct role for VEGF in the pathogenesis of proteinuria has not been demonstrated. METHODS: Expression of VEGF and its receptors (VEGFR-1 and VEGFR-2) was examined in passive Heymann nephritis (PHN) and puromycin aminonucleoside nephrosis (PAN), by immunohistochemistry, in situ hybridization, Northern and Western blotting. Inhibition of VEGF in the PAN model was performed by administration of a blocking antibody. RESULTS: In both models, glomeruli showed upregulation of VEGF and VEGF receptors compared to control animals. VEGF mRNA was increased most significantly (5-fold) at day 5 after induction of PHN, prior to the onset of proteinuria, with persistent upregulation (3-fold) at day 21. Increased VEGF mRNA was also seen in PAN, but it was less marked. In situ hybridization and immunohistochemistry localized VEGF predominantly to podocytes. Increased expression of VEGFR-1 and VEGFR-2 protein was seen in glomerular endothelial cells of PHN and PAN rats by immunohistochemistry, as was VEGFR-2 mRNA by in situ hybridization. Upregulation of VEGFR-1 by endothelial cells was more striking in the PAN model than PHN. Administration of a blocking antibody to rats with PAN did not affect proteinuria, creatinine clearance or sodium excretion. CONCLUSION: The expression of VEGF and its receptors is significantly increased in the PHN and PAN rat models of proteinuria suggesting a role for VEGF in the disease process. VEGF may have an important role in promoting glomerular repair in a variety of glomerular diseases. Copyright 2004 S. Karger AG, Basel",
author = "John Kanellis and Vicki Levidiotis and Khong, {Tiffany Tee Fern} and Cox, {Alison J} and Stacker, {Steven A} and Gilbert, {Richard E} and Cooper, {Mark E} and Power, {David A}",
year = "2004",
doi = "10.1159/000075577",
language = "English",
volume = "96",
pages = "26 -- 36",
journal = "Nephron",
issn = "1660-8151",
publisher = "S Karger AG",
number = "1",

}

Kanellis, J, Levidiotis, V, Khong, TTF, Cox, AJ, Stacker, SA, Gilbert, RE, Cooper, ME & Power, DA 2004, 'A study of VEGF and its receptors in two rat models of proteinuria' Nephron Physiology, vol. 96, no. 1, pp. 26 - 36. https://doi.org/10.1159/000075577

A study of VEGF and its receptors in two rat models of proteinuria. / Kanellis, John; Levidiotis, Vicki; Khong, Tiffany Tee Fern; Cox, Alison J; Stacker, Steven A; Gilbert, Richard E; Cooper, Mark E; Power, David A.

In: Nephron Physiology, Vol. 96, No. 1, 2004, p. 26 - 36.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A study of VEGF and its receptors in two rat models of proteinuria

AU - Kanellis, John

AU - Levidiotis, Vicki

AU - Khong, Tiffany Tee Fern

AU - Cox, Alison J

AU - Stacker, Steven A

AU - Gilbert, Richard E

AU - Cooper, Mark E

AU - Power, David A

PY - 2004

Y1 - 2004

N2 - BACKGROUND: The high level of expression of vascular endothelial growth factor (VEGF) in normal podocyte foot processes suggests that VEGF has an important role in maintaining normal glomerular function. While altered VEGF expression occurs in many glomerular diseases, a direct role for VEGF in the pathogenesis of proteinuria has not been demonstrated. METHODS: Expression of VEGF and its receptors (VEGFR-1 and VEGFR-2) was examined in passive Heymann nephritis (PHN) and puromycin aminonucleoside nephrosis (PAN), by immunohistochemistry, in situ hybridization, Northern and Western blotting. Inhibition of VEGF in the PAN model was performed by administration of a blocking antibody. RESULTS: In both models, glomeruli showed upregulation of VEGF and VEGF receptors compared to control animals. VEGF mRNA was increased most significantly (5-fold) at day 5 after induction of PHN, prior to the onset of proteinuria, with persistent upregulation (3-fold) at day 21. Increased VEGF mRNA was also seen in PAN, but it was less marked. In situ hybridization and immunohistochemistry localized VEGF predominantly to podocytes. Increased expression of VEGFR-1 and VEGFR-2 protein was seen in glomerular endothelial cells of PHN and PAN rats by immunohistochemistry, as was VEGFR-2 mRNA by in situ hybridization. Upregulation of VEGFR-1 by endothelial cells was more striking in the PAN model than PHN. Administration of a blocking antibody to rats with PAN did not affect proteinuria, creatinine clearance or sodium excretion. CONCLUSION: The expression of VEGF and its receptors is significantly increased in the PHN and PAN rat models of proteinuria suggesting a role for VEGF in the disease process. VEGF may have an important role in promoting glomerular repair in a variety of glomerular diseases. Copyright 2004 S. Karger AG, Basel

AB - BACKGROUND: The high level of expression of vascular endothelial growth factor (VEGF) in normal podocyte foot processes suggests that VEGF has an important role in maintaining normal glomerular function. While altered VEGF expression occurs in many glomerular diseases, a direct role for VEGF in the pathogenesis of proteinuria has not been demonstrated. METHODS: Expression of VEGF and its receptors (VEGFR-1 and VEGFR-2) was examined in passive Heymann nephritis (PHN) and puromycin aminonucleoside nephrosis (PAN), by immunohistochemistry, in situ hybridization, Northern and Western blotting. Inhibition of VEGF in the PAN model was performed by administration of a blocking antibody. RESULTS: In both models, glomeruli showed upregulation of VEGF and VEGF receptors compared to control animals. VEGF mRNA was increased most significantly (5-fold) at day 5 after induction of PHN, prior to the onset of proteinuria, with persistent upregulation (3-fold) at day 21. Increased VEGF mRNA was also seen in PAN, but it was less marked. In situ hybridization and immunohistochemistry localized VEGF predominantly to podocytes. Increased expression of VEGFR-1 and VEGFR-2 protein was seen in glomerular endothelial cells of PHN and PAN rats by immunohistochemistry, as was VEGFR-2 mRNA by in situ hybridization. Upregulation of VEGFR-1 by endothelial cells was more striking in the PAN model than PHN. Administration of a blocking antibody to rats with PAN did not affect proteinuria, creatinine clearance or sodium excretion. CONCLUSION: The expression of VEGF and its receptors is significantly increased in the PHN and PAN rat models of proteinuria suggesting a role for VEGF in the disease process. VEGF may have an important role in promoting glomerular repair in a variety of glomerular diseases. Copyright 2004 S. Karger AG, Basel

UR - http://content.karger.com/produktedb/produkte.asp?typ=pdf&file=NEP2004096001026

U2 - 10.1159/000075577

DO - 10.1159/000075577

M3 - Article

VL - 96

SP - 26

EP - 36

JO - Nephron

JF - Nephron

SN - 1660-8151

IS - 1

ER -