A New Look at Platelet-Derived Growth Factor in Renal... : Journal of the American Society of Nephrology (original) (raw)
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Floege, Ju[Combining Diaeresis]rgen*; Eitner, Frank*; Alpers, Charles E.†
*Department of Nephrology and Clinical Immunology, Rheinisch Westfa[Combining Diaeresis]lische Technische Hochschule University Hospital Aachen, Aachen, Germany; and †Department of Pathology, University of Washington, Seattle, Washington
Correspondence: Dr. Ju[Combining Diaeresis]rgen Floege, Department of Nephrology and Clinical Immunology, University Hospital Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany. Phone: +49-241-8089530; Fax: +49-241-8082446; E-mail: [email protected]
Abstract
The PDGF system, comprising four isoforms (PDGF-A, -B, -C, and -D) and two receptor chains (PDGFR-α and -β), 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-β results in an absent glomerular mesangium, whereas PDGF-C and PDGFR-α 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.
Copyright © 2008 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
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