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

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176 Citations (Scopus)

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
Pages (from-to)724-735
Number of pages12
JournalJournal of the American Society of Nephrology
Volume17
Issue number3
DOIs
Publication statusPublished - 2006
Externally publishedYes

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