Role of platelet-derived growth factor in mesangium development and vasculopathies: lessons from platelet-derived growth factor and platelet-derived growth factor receptor mutations in mice.
OBJECTIVE
The phenotypic consequences of null mutations in the platelet-derived growth factor-B and the platelet-derived growth factor beta-receptor genes in mice have demonstrated that these proteins play pivotal roles in the development of the vascular smooth muscle cell lineage, including pericytes and mesangial cells.


RESULTS
The lethality of these mutants has precluded analysis of the physiological and pathophysiological consequences of platelet-derived growth factor-B and platelet-derived growth factor beta-receptor deficiency in adults. This review summarizes and discusses recent data from certain tissue-specific and subtle mutations in the platelet-derived growth factor-B and platelet-derived growth factor beta-receptor genes that are compatible with postnatal viability in spite of severe developmental deficits in pericyte and mesangial cell recruitment. In the postnatal period, the animals studied developed a characteristic set of pathological changes to small blood vessels of the retina and the kidney glomerulus, which sheds light on the importance of pericytes and mesangial cells for vascular integrity and function after birth.


CONCLUSIONS
These microvascular abnormalities and their consequences bear a resemblance to diabetic microangiopathy and nephropathy. The platelet-derived growth factor-B and platelet-derived growth factor beta-receptor mutant mouse models, therefore, might serve as valuable tools in the dissection of some of the pathogenic events in diabetic microangiopathy.
Betsholtz
Christer
C
Department of Medical Biochemistry, University of Göteborg, Sweden. Christer.Betsholtz@medkem.gu.se
Lindblom
Per
P
Bjarnegard
Mattias
M
Enge
Maria
M
Gerhardt
Holger
H
Lindahl
Per
P
D000818:Animals; D005920:Glomerular Mesangium / Q000254:growth & development* / Q000502:physiology*; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology; D007674:Kidney Diseases / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D019899:Paracrine Communication; D020286:Pericytes / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology*; D031300:Retinal Vasculitis / Q000235:genetics / Q000473:pathology; D014652:Vascular Diseases / Q000209:etiology / Q000473:pathology*
D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor