부산대학교 도서관

SUMMARY: Platelet-derived growth factor (PDGF) is a major mesenchymal cell mitogen, with an established role in the pathogenesis of experimental mesangial proliferative nephritis. The role of PDGF in experimental models of crescentic glomerulonephritis is not well defined. To study the role of PDGF in glomerular crescent formation, we induced a model of crescentic glomerulonephritis in transgenic mice expressing high concentrations of the soluble external domain of the PDGFβ receptor (PDGF-Rβ). Crescentic nephritis was induced by the intraperitoneal injection of antibody to whole rabbit glomeruli. At day 7 of disease, biopsies of transgenic and wild-type mice were evaluated for crescent frequency, crescent area, and thickness of crescent cell layer. In situ hybridization was performed to evaluate the expression of both PDGF B-chain and PDGFRβ 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, crescent area quantified by computer image analysis was significantly reduced in transgenic mice (P< 0.015). Transgenic biopsies displayed predominantly crescents composed of two cell layers (P-0.03 compared with wild type), whereas wild-type biopsies had significantly more crescents composed of four or more cell layers (P-0.04). Both PDGF B-chain and PDGF-RβmRNA were detected within crescents in a heterogeneous fashion. Soluble receptor was detectable in the urine of all transgenic diseased mice. We conclude that PDGF plays a role in modulating crescent size and development in our murine model of crescentic nephritis. [ABSTRACT FROM AUTHOR]