Expression of basic fibroblast growth factor and its receptor in the progression of rat crescentic glomerulonephritis

Summary: The aim of this study was to examine the relationship of basic fibroblast growth factor (FGF-2) and its receptor (FGF-R) to tubular proliferation, interstitial fibrosis, glomerular cell proliferation and crescent formation in the development of anti glomerular basement membrane (GBM) glomerulonephrids in the rat. Using new microwave-based histochemistry techniques, weak constitutive expression of mRNA and protein for FGF-2 and FGF-R was evident in tubules and glomeruli of normal rat kidney. Double and triple staining with the proliferating cell nuclear antigen (PCNA) demonstrated that in disease there was focal up-regulation of FGF-2 and FGF-R mRNA and protein expression within proliferating tubules and fibroblast-like cells in areas of interstitial fibrosis. In contrast, tubules in non-inflamed areas of kidney showed no change in FGF-2 and FGF-R expression or cellular proliferation. In addition, many FGF-2⁺PCNA⁺ and FGF-R⁺PCNA⁺ cells, probably mesangial cells and podocytes, were evident within glomerular segmental proliferative lesions. of particular interest was the observation that many epithelial cells within cellular crescents, inculding proliferating (PCNA⁺) epithelial cells, strongly expressed both FGF-2 and FGF-R. Furthermore, there was strong FGF-2 and FGF-R expression by proliferating fibroblast-like cells within fibrocellular crescents suggesting that FGF-2 is involved in the formation and fibrotic progression of glomerular crescents. In conclusion, this study provides evidence that increased expression of FGF-2 and its receptor may participate in the proliferative/fibrotic response in progressive crescentic glomerulonephritis.