PT  - JOURNAL ARTICLE
AU  - Eremina, Vera
AU  - Cui, Shiying
AU  - Gerber, Hanspeter
AU  - Ferrara, Napoleone
AU  - Haigh, Jody
AU  - Nagy, Andras
AU  - Ema, Masatsugu
AU  - Rossant, Janet
AU  - Jothy, Serge
AU  - Miner, Jeffrey H.
AU  - Quaggin, Susan E.
TI  - Vascular Endothelial Growth Factor A Signaling in the Podocyte-Endothelial Compartment Is Required for Mesangial Cell Migration and Survival
AID  - 10.1681/ASN.2005080810
DP  - 2006 Mar 01
TA  - Journal of the American Society of Nephrology
PG  - 724--735
VI  - 17
IP  - 3
4099  - http://jasn.asnjournals.org/content/17/3/724.short
4100  - http://jasn.asnjournals.org/content/17/3/724.full
SO  - J. Am. Soc. Nephrol.2006 Mar 01; 17
AB  - 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 (VEGFhypo/loxP,Neph-Cre+/−) were generated; in these mice, the “allelic dose” of VEGF-A is intermediate between glomerular-specific heterozygous and null states. VEGFhypo/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 (VEGFloxP/loxP,Cre+/−). Together, these results demonstrate a key role for VEGF-A production in the podocyte for mesangial cell survival and differentiation.