| First Author | Eremina V | Year | 2006 |
| Journal | J Am Soc Nephrol | Volume | 17 |
| Issue | 3 | Pages | 724-35 |
| PubMed ID | 16436493 | Mgi Jnum | J:129132 |
| Mgi Id | MGI:3768724 | Doi | 10.1681/ASN.2005080810 |
| Citation | Eremina V, et al. (2006) Vascular endothelial growth factor a signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival. J Am Soc Nephrol 17(3):724-35 |
| abstractText | 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. |
