Fibroblast growth factor 2 and transforming growth factor beta 1 interactions in human liver myofibroblasts.

Abstract

During liver fibrogenesis, myofibroblastic liver cells proliferate and synthesize components of fibrosis. Fibroblast growth factor 2 (FGF-2) is expressed in vivo in myofibroblastic liver cells (MFLCs) during fibrogenesis, and exogenous FGF-2 is mitogenic for MFLCs. The aim of this study was to study the expression and role of endogenous FGF-2 in cultured human MFLCs. FGF-2 and FGF-2 receptors were studied using immunoblotting. All RNA studies used ribonuclease protection. Growth of MFLCs was studied using [3H]thymidine incorporation and direct cell counting. MFLCs expressed FGF-2 and its receptors FGF receptor 1 and FGF receptor 2. An antibody to FGF-2 blocked the mitogenic effect of transforming growth factor beta 1 (TGF-beta 1) for MFLCs but not TGF-beta 1-induced increase in cellular fibronectin 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 of TGF-beta 1. The present results show that anti-FGF-2 and anti-PDGF-AA are not additive and that FGF-2 and PDGF-AA are not sequentially induced by TGF-beta 1. 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.