Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall.
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.
Lindblom
Per
P
Department of Medical Biochemistry, Göteborg University, Göteborg SE-405 30, Sweden.
Gerhardt
Holger
H
Liebner
Stefan
S
Abramsson
Alexandra
A
Enge
Maria
M
Hellstrom
Mats
M
Backstrom
Gudrun
G
Fredriksson
Simon
S
Landegren
Ulf
U
Nystrom
Henrik C
HC
Bergstrom
Goran
G
Dejana
Elisabetta
E
Ostman
Arne
A
Lindahl
Per
P
Betsholtz
Christer
C
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
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