A new look at platelet-derived growth factor in renal disease.
The PDGF system, comprising four isoforms (PDGF-A, -B, -C, and -D) and two receptor chains (PDGFR-alpha and -beta), plays important roles in wound healing, atherosclerosis, fibrosis, and malignancy. Components of the system are expressed constitutively or inducibly in most renal cells. They regulate a multitude of pathophysiologic events, ranging from cell proliferation and migration to extracellular matrix accumulation, production of pro- and anti-inflammatory mediators, tissue permeability, and regulation of hemodynamics. Genetic deletion of PDGF-B or PDGFR-beta results in an absent glomerular mesangium, whereas PDGF-C and PDGFR-alpha contribute to the formation of the renal cortical interstitium. Almost all experimental and human renal diseases are characterized by altered expression of components of the PDGF system. Infusion or systemic overexpression of PDGF-B or -D induces prominent mesangioproliferative changes and renal fibrosis. Intervention studies identified PDGF-C as a mediator of renal interstitial fibrosis and PDGF-B and -D as key factors involved in mesangioproliferative disease and renal interstitial fibrosis. These data establish PDGF as one of the best characterized growth factors in renal disease and the most potent stimulus of mesangial cell proliferation currently identified. Accordingly, targeted intervention against the various PDGF isoforms offers a promising novel therapeutic approach to renal disease.
Floege
Jürgen
J
Department of Nephrology and Clinical Immunology, University Hospital Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany. juergen.floege@rwth-aachen.de
Eitner
Frank
F
Alpers
Charles E
CE
D019281:Dimerization; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000097:blood; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000097:blood; D015398:Signal Transduction
D010982:Platelet-Derived Growth Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta