Basic fibroblast growth factor-binding domain of heparan sulfate in the human glomerulosclerosis and renal tubulointerstitial fibrosis

Lab Invest. 1994 Oct;71(4):528-35.

Abstract

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.

Experimental design: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Fibroblast Growth Factor 2 / analysis*
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / physiology*
  • Glomerulosclerosis, Focal Segmental / metabolism*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Heparitin Sulfate / analysis
  • Heparitin Sulfate / chemistry*
  • Heparitin Sulfate / metabolism
  • Humans
  • Immunohistochemistry
  • Kidney Glomerulus / chemistry
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Male
  • Middle Aged
  • Nephritis, Interstitial / metabolism*
  • Nephritis, Interstitial / pathology

Substances

  • Fibroblast Growth Factor 2
  • Heparitin Sulfate