Growth factor and procollagen type I gene expression in human liver disease

Background/Aims : Growth factors have been implicated in the pathogenesis of liver fibrosis, a major determinant of the clinical course of chronic liver disease. The aim of this study was to study the relationship of growth factor expression to inflammation and fibrosis in a variety of human liver diseases. Methods : We studied by in situ hybridization the expression of transforming growth factor (TGF) β1, platelet-derived growth factor (PDGF) A and PDGF-B, and procollagen type I (pro-I) messenger RNAs (mRNAs) in liver diseases of various etiologies. Results : Pro-I mRNA was expressed by mesenchymal cells at sites of inflammation and scarring, where TGF-β1 immunoreactivity was often found, and by perisinusoidal cells. TGF-β1 and PDGF-A mRNAs were expressed mainly by mononuclear cells and proliferating ductular cells. TGF-β1 mRNA was also expressed by perisinusoidal cells. PDGF-A gene expression was more common than that of PDGF-B. Pro-I and TGF-β1 expression correlated with both ductular proliferation and tissue inflammation, whereas PDGF-A and PDGF-B only correlated with ductular proliferation. Conclusions : Our data suggest that TGF-β1 and PDGF are involved in human liver inflammation and fibrosis. The expression of growth factor mRNAs in proliferating ductular cells may indicate a role for these cells in liver fibrogenesis and may help explain the pathophysiology of conditions such as biliary atresia progressing to fibrosis despite the absence of marked inflammation.