Receptor phenotype underlies differential response of hepatocytes and nonparenchymal cells to heparin-binding fibroblast growth factor type 1 (aFGF) and type 2 (bFGF).
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.
Kan
M
M
W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12946.
Yan
G C
GC
Xu
J
J
Nakahara
M
M
Hou
J
J
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation; D015603:Keratinocytes / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008115:Liver Regeneration; D010641:Phenotype; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor
D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1