Receptor phenotype underlies differential response of hepatocytes and nonparenchymal cells to heparin-binding fibroblast growth factor type 1 (aFGF) and type 2 (bFGF)

In Vitro Cell Dev Biol. Jul-Aug 1992;28A(7-8):515-20. doi: 10.1007/BF02634135.

Abstract

Heparin-binding fibroblast growth factors (HBGF) have been implicated in the regeneration of both parenchymal and nonparenchymal cells of the liver. The response to and phenotype of hepatocyte receptors for HBGF-1 (acidic fibroblast growth factor) and HBGF-2 (basic fibroblast growth factor) were compared to keratinocytes, fibroblasts, and endothelial cells. HBGF-1 stimulated DNA synthesis in hepatocytes, keratinocytes, fibroblasts, and endothelial cells whereas activity of HBGF-2 was limited to fibroblasts and endothelial cells. HBGF-2 antagonized the mitogenic activity of HBGF-1 for hepatocytes and keratinocytes. Hepatocytes and keratinocytes exhibited both high- and low-affinity, nonmatrix receptor sites for HBGF-1, but only low-affinity sites for HBGF-2. The mesenchymal cells displayed only high-affinity sites for both HBGF-1 and HBGF-2. Northern blot and immunochemical analysis revealed that the expression of HBGF receptor genes bek and flg are partitioned between normal hepatocytes and nonparenchymal cells, respectively. Expression of epithelial cell-specific, mesenchymal cell-derived HBGF-7 (keratinocyte growth factor) mRNA in regenerating liver tissue was undetectable relative to HBGF-1. The results support a multifunctional role of HBGF-1 acting through different receptor phenotypes in hepatocyte and nonparenchymal cells during liver regeneration.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cells, Cultured / drug effects
  • Endothelium / drug effects
  • Fibroblast Growth Factor 1 / pharmacology*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblasts / drug effects
  • Gene Expression Regulation
  • Keratinocytes / drug effects
  • Liver / chemistry
  • Liver / drug effects*
  • Liver Regeneration
  • Phenotype
  • Rats
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / genetics
  • Receptors, Fibroblast Growth Factor

Substances

  • Receptors, Cell Surface
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1