학술논문

Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities
Document Type
Source
Development: For advances in developmental biology and stem cells. 131(8):1847-1857
Subject
PDGFB
Cre
loxP
microaneurysm
pericytes
endothelium
Naturvetenskap
Biologi
Utvecklingsbiologi
Natural Sciences
Biological Sciences
Developmental Biology
Language
English
ISSN
1477-9129
Abstract
Platelet-derived growth factor-B (PDGFB) is necessary for normal cardiovascular development, but the relative importance of different cellular sources of PDGFB has not been established. Using Cre-lox techniques, we show here that genetic ablation of Pdgfb in endothelial cells leads to impaired recruitment of pericytes to blood vessels. The endothelium-restricted Pdgfb knockout mutants also developed organ defects including cardiac, placental and renal abnormalities. These defects were similar to those observed in Pdgfb null mice. However, in marked contrast to the embryonic lethality of Pdgfb null mutants, the endothelium-specific mutants survived into adulthood with persistent pathological changes, including brain microhemorrhages, focal astrogliosis, and kidney glomerulus abnormalities. This spectrum of pathological changes is reminiscent of diabetic microangiopathy, suggesting that the endothelium-restricted Pdgfb knockouts may serve as models for some of the pathogenic events of vascular complications to diabetes.