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Human Podocytes Express Angiopoietin 1, a Potential Regulator of Glomerular Vascular Endothelial Growth Factor

Simon C. Satchell^*, Steve J. Harper^*, John E. Tooke, Dontscho Kerjaschki, Moin A. Saleem^* and Peter W. Mathieson^*

*Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom; School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, United Kingdom; and Department of Pathology, University of Vienna-Allgemeines Krakenhaus, Vienna, Austria.

Correspondence to Dr. Simon C. Satchell, Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK. Phone: 44-11-7959-5431; Fax: 44-11-7959-5438; E-mail: s.c.satchell{at}doctors.org.uk

Abstract

ABSTRACT. Vascular endothelial growth factor (VEGF) is abundantly expressed by podocytes, but its role in glomeruli is unknown. Angiopoietins are endothelial cell growth factors that function in concert with VEGF but have not previously been observed in human glomeruli. Angiopoietin 1 (Ang1) acts via the endothelial receptor Tie2 to promote maturation and stabilization of blood vessels, resisting angiogenesis and opposing some actions of VEGF. Ang1, Ang2, Tie2, and VEGF expression in normal human renal cortex was examined with immunofluorescence and immunohistochemical analyses. High-power, multiple-color, immunofluorescence analyses and additional antibodies (specific for particular components of the glomerular filtration barrier) were used to determine the exact locations of Ang1 and Tie2 in the glomerular capillary wall. Immuno-electron-microscopic analysis of rat glomeruli was used to further localize endothelial Tie2 expression. RNA and protein extracted from human glomeruli, cultured human podocytes, and cultured human endothelial cells were analyzed for Ang1, Ang2, and Tie2 by using reverse transcription-PCR and Western blotting. Ang1 was detected in podocytes in normal glomeruli and, with VEGF, was concentrated in podocyte foot processes. Tie2 was demonstrated on glomerular capillary endothelial cells, particularly on the abluminal surface. Reverse transcription-PCR and Western blotting analyses confirmed the expression of Ang1 and Tie2 in glomeruli and of Ang1 in cultured podocytes. These findings suggest a role for Ang1 in the maintenance of the glomerular endothelium and make it a good candidate to be a regulator of the actions of VEGF on glomerular permeability, resisting angiogenesis while allowing the induction of high permeability to water and small solutes.

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