Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall
- Per Lindblom1,
- Holger Gerhardt1,
- Stefan Liebner3,
- Alexandra Abramsson1,
- Maria Enge1,
- Mats Hellström4,
- Gudrun Bäckström5,
- Simon Fredriksson6,
- Ulf Landegren6,
- Henrik C. Nyström2,
- Göran Bergström2,
- Elisabetta Dejana3,
- Arne Östman5,
- Per Lindahl1, and
- Christer Betsholtz1,7
- 1 Department of Medical Biochemistry, Göteborg University, Göteborg SE-405 30, Sweden
- 2 Department of Physiology, Göteborg University, Göteborg SE-405 30, Sweden
- 3 FIRC Institute of Molecular Oncology, Milan 20139, Italy
- 4 Angiogenetics AB, Göteborg SE-405 30, Sweden
- 5 Ludwig Institute for Cancer Research, Uppsala SE-751 24, Sweden
- 6 The Beijer Laboratory, Department of Genetics and Pathology, Uppsala University, Uppsala SE-751 85, Sweden
Abstract
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.
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Footnotes
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Corresponding author.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.266803.
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↵7 E-MAIL Christer.Betsholtz{at}medkem.gu.se; FAX 46-31-416108.
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- Accepted May 23, 2003.
- Received April 3, 2003.
- Cold Spring Harbor Laboratory Press
