Downregulation of matrix and beta-PDGF receptor gene expression by anti-TGF beta antibody in rat hepatic stellate cells during experimental liver injury

Excess matrix in hepatic fibrosis results from both fibrogenic stimulation of stellate cells by TGF beta 1 and cell proliferation due to induction of beta-platelet derived growth factor receptor (beta-PDGFR). In this paper, treatment of culture-activated rat stellate cells with anti-TGF beta inhibited collagen and fibronectin mRNA expression by 82 and 58%, respectively, versus control cells. In vivo, anti-TGF beta inhibited collagen I gene expression by 86% in stellate cells isolated from rats treated with CC14 compared with control antibody. In contrast to stellate cells, anti-TGF beta had no effect on collagen I gene expression in isolated sinusoidal endothelial cells. Anti-TGF beta administered in vivo to rats with liver injury also reduced expression of stellate cell beta-PDGFR mRNA to that of control animals. Anti-TGF beta antibody had no effect on the histologic appearance of the tissue. These data support a role for TGF beta in stellate cell matrix expression and provide evidence for transmodulation of PDGF receptor by TGF beta in vivo. However, inhibition of TGF beta alone may not be adequate to attenuate severe hepatic injury and fibrosis. (C) 1997 Elsevier Science Ireland Ltd.