In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis

• Type of Material: Article
• Authors: Mark Czaja, Emory University; Francis R. Weiner, Albert Einstein College of Medicine; Kathleen C. Flanders, Albert Einstein College of Medicine; Marei-Adele Giambrone, Albert Einstein College of Medicine; Robert Wind, Albert Einstein College of Medicine; Luis Biempica, Albert Einstein College of Medicine; Mark A. Zern, Albert Einstein College of Medicine
• Language: English
• Date: 1989-06-01
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: The Rockefeller University Press
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1083/jcb.108.6.2477
• Title of Journal or Parent Work: Journal of Cell Biology
• ISSN: 0021-9525
• Volume: 108
• Issue: 6
• Start Page: 2477
• End Page: 2482
• Grant/Funding Information: This investigation was supported in part by National Institutes of Health Grants AA-06386, AM-38484, and DK-01792; an American Liver Foundation Fellowship Award to M. J. Czaja; a Sinsheimer Foundation Award to M. A. Zern; and an Irma T. Hirschl Career Scientist Award to M. A. Zern.
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cell Biology
• Research Categories: Biology, Cell

Abstract

Despite extensive efforts, little progress has been made in identifying the factors that induce hepatic fibrosis. Transforming growth factor-β (TGF-β) has been shown to enhance collagen production, therefore its role in hepatic fibrosis was investigated. Treatment of cultured hepatic cells with TGF-β1 increased type I procollagen mRNA levels 13-fold due to post-transcriptional gene regulation. When two animal models of hepatic fibrosis, murine schistosomiasis and CCl4-treated rats, were examined, they both exhibited increased levels of TGF-β1 gene expression at times that somewhat preceded the increase in collagen synthesis. In contrast, in murine schistosomiasis, mRNA levels of tumor necrosis factor and interleukin-1 peaked early in the fibrogenic process. Immunohistochemical analysis showed TGF-β1 to be present in normal mouse liver and to be markedly increased in mice infected with schistosomiasis. TGF-β1 appeared in the hepatic parenchyma, primarily in hepatocytes. These findings strongly suggest a role for TGF-β1 in a pathophysiological state.