The role of platelet-derived growth factor in a murine model of crescenticnephritis

Platelet-derived growth factor (PDGF) is a major mesenchymal cell mitogen, with an established role in the pathogenesis of experimental mesangial prol iferative nephritis. The role of PDGF in experimental models of crescentic glomerulonephritis is not well defined. To study the role of PDGF in glomer ular crescent formation, we induced a model of crescentic glomerulonephriti s in transgenic mice expressing high concentrations of the soluble external domain of the PDGF beta receptor (PDGF-R beta). Crescentic nephritis was i nduced by the intraperitoneal injection of antibody to whole rabbit glomeru li. At day 7 of disease, biopsies of transgenic and wild-type mice were eva luated for crescent frequency, crescent area, and thickness of crescent cel l layer. In situ hybridization was performed to evaluate the expression of both PDGF B-chain and PDGFR beta mRNA within crescents. Delivery of soluble receptor to the urinary space was evaluated by Western blotting. Crescent frequency did not differ between wild type and transgenic mice. However, cr escent area quantified by computer image analysis was significantly reduced in transgenic mice (P < 0.015). Transgenic biopsies displayed predominantl y crescents composed of two cell layers (P = 0.03 compared with wild type), whereas wild-type biopsies had significantly more crescents composed of fo ur or more cell layers (P = 0.04). Both PDGF B-chain and PDGF-R beta mRNA w ere detected within crescents in a heterogeneous fashion. Soluble receptor was detectable in the urine of all transgenic diseased mice. We conclude th at PDGF plays a role in modulating crescent size and development in our mur ine model of crescentic nephritis.