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) proteoglycans show enormous complexity. These polysaccharides can interact specifically with cytokines such as basic fibroblast growth factor (bFGF). The understanding of HS expression in glomerulosclerosis and interstitial fibrosis, which is still rudimentary, could provide some insight about the role of bFGF in kidney diseases.


METHODS
Kidney sections were exposed to exogenous bFGF and then to a monoclonal anti-bFGF antibody. Specificity of the interaction between HS and bFGF was established by monitoring concomitant loss of bFGF during selective removal of HS with heparitinase and competitive inhibition studies. To further characterize regional changes in saccharide sequences, heparitinase-generated unsaturated disaccharides, N-sulfated glucosamine-enriched but O-sulfate-scarce portions characteristics of native HS, and such portions characteristic of Engelbreth-Holm-Swarm tumor HS were studied.


RESULTS
HS was detected in interstitial fibrosis and in advanced glomerulosclerosis, whereas bFGF-binding domains were found only in the fibrosis: The distributional pattern of the N-sulfate-enriched and O-sulfate-scarce portions of native HS was similar to that of bFGF-binding domains. Moreover, a small population of parenchymal cells in advanced tubulointerstitial fibrosis with marked cellular infiltration were especially rich in the bFGF-binding domains.


CONCLUSIONS
In fibrotic lesions of the peritubular interstitium, HS shows enrichment of bFGF-binding domains. These regions may play an important role in the fibrogenesis through their interaction with endogenous bFGF.
Branch Hospital, Nagoya, Japan.
H
H
Morita
T
T
Shinzato
G
G
David
A
A
Mizutani
H
H
Habuchi
Y
Y
Fujita
M
M
Ito
J
J
Asai
K
K
Maeda
K
K
Kimata
D000328:Adult; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000378:metabolism / Q000502:physiology*; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology; D006497:Heparan Sulfate / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000378:metabolism* / Q000473:pathology
D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate