title: Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall.
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.
authors.affiliation: Department of Medical Biochemistry, Göteborg University, Göteborg SE-405 30, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Lindblom
authors.forename: Holger
authors.initials: H
authors.lastname: Gerhardt
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Abramsson
authors.forename: Maria
authors.initials: M
authors.lastname: Enge
authors.forename: Mats
authors.initials: M
authors.lastname: Hellstrom
authors.forename: Gudrun
authors.initials: G
authors.lastname: Backstrom
authors.forename: Simon
authors.initials: S
authors.lastname: Fredriksson
authors.forename: Ulf
authors.initials: U
authors.lastname: Landegren
authors.forename: Henrik C
authors.initials: HC
authors.lastname: Nystrom
authors.forename: Goran
authors.initials: G
authors.lastname: Bergstrom
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
authors.forename: Arne
authors.initials: A
authors.lastname: Ostman
authors.forename: Per
authors.initials: P
authors.lastname: Lindahl
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008833:Microcirculation / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D020286:Pericytes / Q000378:metabolism*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011507:Proteinuria / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics* / Q000378:metabolism*; D012160:Retina / Q000378:metabolism / Q000502:physiology; D012162:Retinal Degeneration / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors