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

Giuseppe Malizia, Elizabeth M. Brunt, Marion G. Peters, Aroldo Rizzo, Thomas J. Broekelmann, John A. McDonald

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)145-156
Number of pages12
JournalGastroenterology
Volume108
Issue number1
DOIs
StatePublished - Jan 1995

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