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

Journal article
Authors Per Lindblom
Holger Gerhardt
Stefan Liebner
Alexandra Abramsson
Maria Enge
Mats Hellström
Gudrun Bäckström
Simon Fredriksson
Ulf Landegren
Henrik Nyström
Göran Bergström
Elisabetta Dejana
Arne Östman
Per Lindahl
Christer Betsholtz
Published in Genes & development
Volume 17
Issue 15
Pages 1835-40
ISSN 0890-9369
Publication year 2003
Published at Wallenberg Laboratory
Institute of Medical Biochemistry
Institute of Physiology and Pharmacology, Dept of Physiology
Pages 1835-40
Language en
Links dx.doi.org/10.1101/gad.266803
Keywords Alleles, Amino Acid Motifs, Amino Acid Sequence, Animals, Cell Movement, Endothelial Growth Factors, metabolism, Endothelium, Vascular, metabolism, Glomerulosclerosis, Focal Segmental, genetics, Intercellular Signaling Peptides and Proteins, metabolism, Kidney, physiology, Lymphokines, metabolism, Mice, Microcirculation, metabolism, Microscopy, Fluorescence, Models, Genetic, Molecular Sequence Data, Mutation, Pericytes, metabolism, Phenotype, Platelet-Derived Growth Factor, metabolism, Protein Structure, Tertiary, Proteinuria, genetics, Proto-Oncogene Proteins c-sis, genetics, metabolism, Retina, metabolism, physiology, Retinal Degeneration, genetics, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors
Subject categories Medical and Health Sciences

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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