BASIC FIBROBLAST GROWTH FACTOR-BINDING DOMAIN OF HEPARAN-SULFATE IN THE HUMAN GLOMERULOSCLEROSIS AND RENAL TUBULOINTERSTITIAL FIBROSIS

BACKGROUND: The saccharide side chains of heparan sulfate (HS) proteog lycans show enormous complexity. These polysaccharides can interact sp ecifically with cytokines such as basic fibroblast growth factor (bFGF ). The understanding of HS expression in glomerulosclerosis and inters titial fibrosis, which is still rudimentary, could provide some insigh t about the role of bFGF in kidney diseases. EXPERIMENTAL DESIGN: Kidn ey sections were exposed to exogenous bFGF and then to a monoclonal an ti-bFGF antibody. Specificity of the interaction between HS and bFGF w as established by monitoring concomitant loss of bFGF during selective removal of HS with heparitinase and competitive inhibition studies. T o further characterize regional changes in saccharide sequences, hepar itinase-generated unsaturated disaccharides, N-sulfated glucosamine-en riched but O-sulfate-scarce portions characteristic of native HS, and such portions characteristic of Engelbreth-Holm-Swarm tumor HS were st udied. RESULTS: HS was detected in interstitial fibrosis and in advanc ed glomerulosclerosis, whereas bEGF-binding domains were found only in the fibrosis: The distributional pattern of the N-sulfate-enriched an d O-sulfate-scarce portions of native HS was similar to that of bFGF-b inding domains. Moreover, a small population of parenchymal cells in a dvanced tubulointerstitial fibrosis with marked cellular infiltration were especially rich in the bFGF-binding domains. CONCLUSIONS: In fibr otic lesions of the peritubular interstitium, HS shows enrichment of b FGF-binding domains. These regions may play an important role in the f ibrogenesis through their interaction with endogenous bFGF.