title: The alternatively spliced anti-angiogenic family of VEGF isoforms VEGFxxxb in human kidney development.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF), required for renal development, is generated by alternative splicing of 8 exons to produce two families, pro-angiogenic VEGF(xxx), formed by proximal splicing in exon 8 (exon 8a), and anti-angiogenic VEGF(xxx)b, generated by distal splicing in exon 8 (exon 8b). VEGF(165)b, the first described exon 8b-containing isoform, antagonises VEGF(165) and is anti-angiogenic in vivo.
  
  
  METHODS
  Using VEGF(xxx)b-specific antibodies, we investigated its expression quantitatively and qualitatively in developing kidney, and measured the effect of VEGF(165)b on renal endothelial and epithelial cells.
  
  
  RESULTS
  VEGF(xxx)b formed 45% of total VEGF protein in adult renal cortex, and VEGF(165)b does not increase glomerular endothelial cell permeability, it inhibits migration, and is cytoprotective for podocytes. During renal development, VEGF(xxx)b 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.
  
  
  CONCLUSIONS
  These results show that the anti-angiogenic VEGF(xxx)b isoforms are highly expressed in adult and developing renal cortex, and suggest that the VEGF(xxx)b family plays a role in glomerular maturation and podocyte protection by regulating the pro-angiogenic pro-permeability properties of VEGF(xxx) isoforms.
authors.affiliation: Microvascular Research Laboratories, Department of Physiology, University of Bristol, Bristol, UK.
authors.forename: Heather S
authors.initials: HS
authors.lastname: Bevan
authors.forename: Nynke M S
authors.initials: NM
authors.lastname: van den Akker
authors.forename: Yan
authors.initials: Y
authors.lastname: Qiu
authors.forename: Japke A E
authors.initials: JA
authors.lastname: Polman
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Foster
authors.forename: Justin
authors.initials: J
authors.lastname: Yem
authors.forename: Ali
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Simon C
authors.initials: SC
authors.lastname: Satchell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Harper
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.forename: David O
authors.initials: DO
authors.lastname: Bates
mesh_terms: D000375:Aging / Q000378:metabolism*; D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics* / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D020033:Protein Isoforms; D022821:RNA Splice Sites; C467485:VEGFB protein, human; D042561:Vascular Endothelial Growth Factor B