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Original Paper

The Alternatively Spliced Anti-Angiogenic Family of VEGF Isoforms VEGFxxxb in Human Kidney Development

Bevan H.S.a · van den Akker N.M.S.c · Qiu Y.a · Polman J.A.E.c · Foster R.R.a · Yem J.a · Nishikawa A.a · Satchell S.C.b · Harper S.J.a · Gittenberger-de Groot A.C.c · Bates D.O.a

Author affiliations

aMicrovascular Research Laboratories, Department of Physiology, University of Bristol, and bAcademic Renal Unit, Southmead Hospital, Bristol, UK; cDepartment of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands

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Nephron Physiol 2008;110:p57

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 12, 2008
Accepted: September 01, 2008
Published online: November 27, 2008
Issue release date: December 2008

Number of Print Pages: 1
Number of Figures: 7
Number of Tables: 0


eISSN: 1660-2137 (Online)

For additional information: https://www.karger.com/NEP

Abstract

Background/Aim: Vascular endothelial growth factor (VEGF), required for renal development, is generated by alternative splicing of 8 exons to produce two families, pro-angiogenic VEGFxxx, formed by proximal splicing in exon 8 (exon 8a), and anti-angiogenic VEGFxxxb, generated by distal splicing in exon 8 (exon 8b). VEGF165b, the first described exon 8b-containing isoform, antagonises VEGF165 and is anti-angiogenic in vivo. Methods: Using VEGFxxxb-specific antibodies, we investigated its expression quantitatively and qualitatively in developing kidney, and measured the effect of VEGF165b on renal endothelial and epithelial cells. Results: VEGFxxxb formed 45% of total VEGF protein in adult renal cortex, and VEGF165b does not increase glomerular endothelial cell permeability, it inhibits migration, and is cytoprotective for podocytes. During renal development, VEGFxxxb was expressed in the condensed vesicles of the metanephros, epithelial cells of the comma-shaped bodies, invading endothelial cells and epithelial cells of the S-shaped body, and in the immature podocytes. Expression reduced as the glomerulus matured. Conclusion: These results show that the anti-angiogenic VEGFxxxb isoforms are highly expressed in adult and developing renal cortex, and suggest that the VEGFxxxb family plays a role in glomerular maturation and podocyte protection by regulating the pro-angiogenic pro-permeability properties of VEGFxxx isoforms.

© 2008 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 12, 2008
Accepted: September 01, 2008
Published online: November 27, 2008
Issue release date: December 2008

Number of Print Pages: 1
Number of Figures: 7
Number of Tables: 0


eISSN: 1660-2137 (Online)

For additional information: https://www.karger.com/NEP


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