Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration.
Heparin-binding growth factor type 1 (HBGF-1; sometimes termed acidic fibroblast growth factor) is potentially an important factor in liver regeneration. HBGF-1 alone (half-maximal effect at 60 pM) stimulated hepatocyte DNA synthesis and bound to a high-affinity receptor (Kd = 62 pM; 5000 per cell). Epidermal growth factor (EGF) neutralized or masked the mitogenic effect of HBGF-1 concurrent with appearance of low-affinity HBGF-1 binding sites. HBGF-1 reduced the inhibitory effect of transforming growth factor type beta (TGF-beta) on the EGF stimulus. Nanomolar levels of HBGF-1 decreased the EGF stimulus. An increase in hepatic HBGF-1 gene expression after partial hepatectomy precedes increases in expression of the EGF homolog, TGF-alpha, and nonparenchymal-cell-derived TGF-beta in the regenerating liver. Expression of HBGF-1 mRNA occurs in both hepatocytes and nonparenchymal cells and persists for 7 days in liver tissue after partial hepatectomy. HBGF-1 acting through a high-affinity receptor is a candidate for the early autocrine stimulus that drives hepatocyte DNA synthesis prior to or concurrent with the EGF/TGF-alpha stimulus. It may allow hepatocyte proliferation to proceed in the presence of low levels of TGF-beta. An EGF/TGF-alpha-dependent change in HBGF-1 receptor phenotype and increasing levels of nonparenchymal-cell-derived HBGF-1 and TGF-beta may serve to limit hepatocyte proliferation.
Kan
M
M
W. Alton Jones Cell Science Center, Inc., Lake Placid, NY 12946.
Huang
J S
JS
Mansson
P E
PE
Yasumitsu
H
H
Carr
B
B
McKeehan
W L
WL
D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology*; D015870:Gene Expression; D005796:Genes; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic; D015291:Transforming Growth Factors / Q000494:pharmacology
D006133:Growth Substances; D008934:Mitogens; D012333:RNA, Messenger; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D006493:Heparin