VEGF receptor 2 blockade leads to renal cyst formation in mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-05

AUTHORS

S McGrath-Morrow, C Cho, R Molls, M Burne-Taney, M Haas, D J Hicklin, R Tuder, H Rabb

ABSTRACT

Polycystic kidney disease (PKD) is associated with mutations in PKD1 and PKD2 and vascular abnormalities. The links between the epithelial and vascular defects, however, are poorly understood. Vascular endothelial growth factor (VEGF) has been shown to be critical for normal kidney development. In animal models, blockade of VEGF in the perinatal period can lead to abnormal glomerular development, impaired nephrogenesis, proteinuria, and renal failure. We hypothesized that brief blockade of VEGF signaling during early postnatal kidney development can lead to renal cyst development. On days 2 and 4 of life, CD-1 mice were treated with antibodies generated against the extracellular portion of the VEGF receptor 2 (DC101), the area of the receptor where VEGF binding occurs. Mice developed renal cysts between 2 and 3 weeks. The DC101-treated mice also had increased cell proliferation in the renal tubule epithelium. In addition, mice receiving DC101 developed abnormal glomeruli, proteinuria, and patchy cellular infiltrates. Early disruption of VEGFR-2 signaling during the perinatal period results in renal cyst formation, impaired glomerulogenesis, and inflammation. VEGF could be a key link between vascular and cystic changes in kidney cyst formation. More... »

PAGES

1741-1748

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.ki.5000314

DOI

http://dx.doi.org/10.1038/sj.ki.5000314

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015725852

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16572116


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