BFGF AND ITS LOW-AFFINITY RECEPTORS IN THE PATHOGENESIS OF HIV-ASSOCIATED NEPHROPATHY IN TRANSGENIC MICE

HIV-associated nephropathy is characterized by extensive tubulointerst itial disease with epithelial cell injury, microcystic proliferation, and tubular regeneration with glomerulosclerosis. To explore the role of bFGF as a mediator of HIV-induced interstitial disease, we utilized an HIV transgenic mouse model that manifests clinical and histologica l features observed in patients. In transgenic mice, simultaneous rena l epithelial cell proliferation and injury were detected in vivo. In a reas of microcystic proliferation, immunoreactive bFGF colocalized wit h extracellular matrix. Kidneys from transgenic mice had increased bFG F low affinity binding sites, particularly in the renal interstitium. In vitro, transgenic renal tubular epithelial cells proliferated more rapidly and generated tubular structures spontaneously, in marked cont rast to nontransgenic renal cells where these pathologic features coul d be mimicked by exogenous bFGF. These studies suggest that renal bFGF and its receptors play an important role in the pathogenesis of HIV-a ssociated nephropathy.