Vascular endothelial growth factor A signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival

Vera Eremina, Shiying Cui, Hanspeter Gerber, Napoleone Ferrara, Jody Haigh, Andras Nagy, Masatsugu Ema, Janet Rossant, Serge Jothy, Jeffrey H. Miner, Susan E. Quaggin*

*Corresponding author for this work

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

The glomerular filtration barrier separates the blood from the urinary space and consists of two major cell types: podocytes and fenestrated endothelial cells. Mesangial cells sit between the capillary loops and provide structural support. Proliferation and loss of mesangial cells both are central findings in a number of renal diseases, including diabetic nephropathy and mesangiolysis, respectively. Using cell-specific gene targeting, it was shown previously that vascular endothelial growth factor A (VEGF-A) production by podocytes is required for glomerular endothelial cell migration, differentiation, and survival. For further investigation of the effect of gene dose and VEGF-A knockdown within the glomerulus, mice that carry one hypomorphic VEGF-A allele and one podocyte-specific null VEGF-A allele (VEGF?,Neph-Cre?) were generated; in these mice, the "allelic dose" of VEGF-A is intermediate between glomerular-specific heterozygous and null states. VEGF hypo/loxP,Neph-Cre+/- mice die at 3 wk of age from renal failure. Although endothelial cell defects are observed, striking loss of mesangial cells occurs postnatally. In addition, differentiated mesangial cells cannot be found in glomeruli of podocyte-specific null VEGF-A mice (VEGF loxP/loxP,Cre+/-). Together, these results demonstrate a key role for VEGF-A production in the podocyte for mesangial cell survival and differentiation.

Original languageEnglish (US)
Pages (from-to)724-735
Number of pages12
JournalJournal of the American Society of Nephrology
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2006

ASJC Scopus subject areas

  • Nephrology

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