Type I procollagen production and cell proliferation is mediated by transforming growth factor-β in a model of hepatic fibrosis

G. Eghbali-Fatourechi, G. C. Sieck, Y. S. Prakash, P. Maercklein, G. J. Gores, L. A. Fitzpatrick

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Fibrosis is a significant component of advanced chronic inflammatory liver diseases and is caused by the accumulation of extracellular matrix, including type I procollagen. The mechanism by which fibrosis develops in liver tissue remains unknown. We tested the effects of transforming growth factor β1 (TGF-β), a cytokine that alters cell differentiation and proliferation, and bleomycin, a cytotoxic glycopeptide antibiotic, on cultured isolated rat hepatocytes, TGF-β (1 ng/ml) inhibited radiolabeled thymidine incorporation 89% at 24 h and 69% at 48 h. Inhibition of hepatocyte proliferation was dose dependent. Bleomycin (1 μg/ml) significantly inhibited radiolabeled thymidine incorporation at 48 h (44%). Neutralizing antibody to TGF-β (TGF- β-Ab) attenuated the inhibition of proliferation by TGF-β and bleomycin in a concentration-dependent manner. The addition of either TGF-β or bleomycin increased immunostaining of type I procollagen in hepatocytes. The addition of TGF-β-Ab alone increased cell proliferation, suggesting that neutralization of endogenous TGF-β may attenuate the inhibition of hepatocyte proliferation. These data suggest that the hepatocyte contains type I procollagen and, under some conditions, produces TGF-β. We propose that procollagen production in rat hepatocytes is induced by TGF-β and may be related to endogenous production of this cytokine in response to cell injury. The cytotoxic effect of bleomycin is mediated by TGF-β and inhibition of TGF-β and bleomycin with TGF-β-Ab attenuates the additive effects of those compounds on isolated rat hepatocytes. These data provide a model of collagen expression in isolated rat hepatocytes.

Original languageEnglish (US)
Pages (from-to)1894-1903
Number of pages10
JournalEndocrinology
Volume137
Issue number5
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Endocrinology

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