title: The platelet-derived growth factor system in renal disease: an emerging role of endogenous inhibitors.
abstract: The platelet-derived growth factor (PDGF) family consists of four isoforms which are secreted as homodimers (PDGF-AA, PDGF-BB, PDGF-CC and PDGF-DD) or heterodimers (PDGF-AB), and two receptor chains (PDGFR-α and -β). All members of the PDGF system are constitutively or inducibly expressed in renal cells and are involved in the regulation of cell proliferation and migration, the accumulation of extracellular matrix proteins and the secretion of pro- and anti-inflammatory mediators. Particular roles have been identified in mediating mesangioproliferative changes, renal interstitial fibrosis and glomerular angiogenesis. Different endogenous inhibitors of PDGF-induced biological responses exist which affect the activation/deactivation of PDGF isoforms, the activity of the PDGFRs, or which block downstream signaling pathways of the autophosphorylated PDGFRs. The novel endogenous inhibitor nephroblastoma overexpressed gene (NOV, CCN3) reduces PDGF-induced cell proliferation and is downregulated by PDGF isoforms itself. Among all identified inhibitors only few "true" PDGF antagonists have been identified. A better understanding of these inhibitors may aid in the design of novel therapeutic approaches to PDGF-mediated diseases.
authors.affiliation: Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany. cvanroeyen@ukaachen.de
authors.forename: Claudia R C
authors.initials: CR
authors.lastname: van Roeyen
authors.forename: Tammo
authors.initials: T
authors.lastname: Ostendorf
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
mesh_terms: D000818:Animals; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010982:Platelet-Derived Growth Factor