Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall.
2003 (English)In: Genes Dev, ISSN 0890-9369, Vol. 17, no 15, 1835-40 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2003. Vol. 17, no 15, 1835-40 p.
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
IdentifiersURN: urn:nbn:se:uu:diva-10797PubMedID: 12897053OAI: oai:DiVA.org:uu-10797DiVA: diva2:38565