Vol. 164, No. 3, 1989 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS November 15, 1989 Pages 1182-1189 CBARACTERIZATION OF A Mr 25,000 BASIC FIBROBLAST GROWTH FACTOR FORM IN ADULT, REGENERATING, AND FETAL RAT LIVER M. Presta, M. Statuto, M. Rusnati, P. Dell'Era, and G. Ragnotti Unit of General Pathology, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, via Valsabbina 19, 25124 Brescia, Italy Received September 1, 1989 SUMMARY: A heparin-binding Mr 25,000 immunoreactive bFGF-like protein (ir- bFGF) is recognized in adult rat liver extract by affinity-purified polyclonal anti-human placental bFGF antibodies. Hepatic levels of this protein increase 4-fold in regenerating rat liver during the first 48 h after partial hepatectomy. Also, they appear to be higher in embryonic than in newborn or in adult rat liver. Mr 25,000 ir-bFGF from regenerating rat liver, partially purified by heparin-affinity chromatography, induces plasminogen activator activity and cell proliferation in transformed fetal bovine aortic endothelial GM 7373 cells and competes with Mr 18,000 [125I]bFGF for the binding to high affinity bFGF receptors. The data indicate the presence in rat liver of a high molecular weight form of bFGF whose expression is modulated during embryonic development and liver regeneration. 0 1989 Academic Press, Inc. Basic fibroblast growth factor (bFGF) is a Mr 18,000 heparin-binding mitogen (1) which has been isolated from a variety of tissues and cell lines (2). However, high molecular weight immunoreactive bFGF-like proteins (ir- bFGFs) have been identified in rat brain and in rat tumor pituitary GH3 cells (3, 4) and a Mr 25,000 bFGF form has been purified from guinea pig brain (5). Moreover, in vitro translation of bFGF mRNA has been shown to generate high molecular weight bFGF forms initiated by alternative CUG codons (6, 7). Thus, more than one molecular form of bFGF exist. Liver regeneration represents an example of synchronized cell replication in vivo. Rat hepatocytes, quiescent in adult animals, undergo proliferation after partial hepatectomy, the peak of DNA synthesis occurring 24 hours after surgery (8). An increase in the expression of several genes, including proto- oncogenes and growth factor genes, has been observed during liver regeneration (9-12). Thus, liver regeneration appears to be a suitable experimental model Abbreviations: ir-bFGF, immunoreactive basic fibroblast growth factor; PA, plasminogen activator. 0006-291x/89 $1.50 Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved. 1182