FIBROBLAST-GROWTH-FACTOR-2 AND TRANSFORMING GROWTH-FACTOR-BETA-1 INTERACTIONS IN HUMAN LIVER MYOFIBROBLASTS

Background & Aims: During liver fibrogenesis, myofibroblastic liver ce lls proliferate and synthesize components of fibrosis, Fibroblast grow th factor 2 (FGF-2) is expressed in vivo in myofibroblastic liver cell s (MFLCs) during fibrogenesis, and exogenous FGF-2 is mitogenic for MF LCs. The aim of this study was to study the expression and role of end ogenous FGF-2 in cultured human MFLCs. Methods: FGF-2 and FGF-2 recept ors were studied using immunoblotting. All RNA studies used ribonuclea se protection, Growth of MFLCs was studied using [H-3]thymidine incorp oration and direct cell counting. Results: MFLCs expressed FGF-2 and i ts receptors FGF receptor 1 and FGF receptor 2. An antibody to FGF-2 b locked the mitogenic effect of transforming growth factor beta 1 (TGF- beta 1) for MFLCs but not TGF-beta 1-induced increase in cellular fibr onectin messenger RNA (mRNA). TGF-beta 1 increased levels of FGF-2 and FGF receptor mRNAs in MFLCs. We have previously shown that TGF-beta 1 also increased platelet-derived growth factor (PDGF) A chain mRNA in these cells and that anti-PDGF antibody blunted the mitogenic effect o f TGF-beta 1. The present results show that anti-FGF-2 and anti-PDGF-A A are not additive and that FGF-2 and PDGF-AA are not sequentially ind uced by TGF-beta 1. Conclusions: FGF-2 mediates the mitogenic but not the profibrogenic effect of TGF-beta 1 for human MFLCs, and autocrine FGF-2 and PDGF-A interact in the mediation of the mitogenic effect of TGF-beta 1.