Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall

被引:494
作者
Lindblom, P
Gerhardt, H
Liebner, S
Abramsson, A
Enge, M
Hellström, M
Bäckström, G
Fredriksson, S
Landegren, U
Nyström, HC
Bergström, G
Dejana, E
Östman, A
Lindahl, P
Betsholtz, C [1 ]
机构
[1] Univ Gothenburg, Dept Med Biochem, SE-40530 Gothenburg, Sweden
[2] Univ Gothenburg, Dept Physiol, SE-40530 Gothenburg, Sweden
[3] FIRC Inst Mol Oncol, I-20139 Milan, Italy
[4] Angiogenet AB, SE-40530 Gothenburg, Sweden
[5] Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden
[6] Uppsala Univ, Dept Genet & Pathol, Beijer Lab, SE-75185 Uppsala, Sweden
关键词
PDGF; cell retention; heparan sulphate proteoglycan; pericyte; mesangial cell; retina;
D O I
10.1101/gad.266803
中图分类号
Q2 [细胞生物学];
学科分类号
071009 [细胞生物学]; 090102 [作物遗传育种];
摘要
Several platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) family members display C-terminal protein motifs that confer retention of the secreted factors within the pericellular space. To address the role of PDGF-B retention in vivo, we deleted the retention motif by gene targeting in mice. This resulted in defective investment of pericytes in the microvessel wall and delayed formation of the renal glomerulus mesangium. Long-term effects of lack of PDGF-B retention included severe retinal deterioration, glomerulosclerosis, and proteinuria. We conclude that retention of PDGF-B in microvessels is essential for proper recruitment and organization of pericytes and for renal and retinal function in adult mice.
引用
收藏
页码:1835 / 1840
页数:6
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