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Podocyte specific over‐expression of VEGF‐A 165 b, unlike VEGF‐A 165 , does not cause collapsing glomerulopathy
Author(s) -
Ferguson Joanne Kathryn,
Qiu Yan,
Neal Chris R,
Sage Leslie,
Bates David O,
Salmon Andrew H J,
Harper Steve
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.926.16
Subject(s) - podocyte , nephrin , glomerulus , medicine , endocrinology , vascular endothelial growth factor , biology , vegf receptors , kidney , proteinuria
Regulation of podocyte expression of vascular endothelial growth factor A (VEGF‐A) is critical for the establishment and maintenance of the glomerular filtration barrier (GFB). Podocyte‐specific VEGF‐A 165 overexpression during development causes collapsing glomerulopathy (Eremina et al, 2003). VEGF‐A 165 contributes to the high water permeability of glomeruli (Salmon et al 2006). Podocytes express both VEGF‐A isoform families: VEGF‐A xxx and VEGF‐A xxx b. We sought to determine the role of VEGF‐A 165 b in the glomerulus, using heterozygous transgenic mice whose podocytes overexpress VEGF‐A 165 b under nephrin promoter control throughout development and adulthood. Glomerular L p A and albumin reflection coefficient (σ) were measured with an oncometric technique. (Salmon et al 2006; Sage et al 2007). Mice appeared healthy until at least 18 months old, with no overt renal phenoytpe. L p A was reduced by 40% compared with glomeruli form wild‐type littermates, but glomerular σ was unchanged. Glomeruli appeared normal by light microscopy, with no evidence of glomerular collapse. Resin embedded Toluidine Blue stained sections showed a disrupted filtration barrier with absence of sub podocyte space. Our results indicate that VEGF‐A 165 b plays a strikingly different role to VEGF‐A 165 in glomerular development and physiology.