TY - JOUR
T1 - Type I procollagen production and cell proliferation is mediated by transforming growth factor-β in a model of hepatic fibrosis
AU - Eghbali-Fatourechi, G.
AU - Sieck, G. C.
AU - Prakash, Y. S.
AU - Maercklein, P.
AU - Gores, G. J.
AU - Fitzpatrick, L. A.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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U2 - 10.1210/endo.137.5.8612529
DO - 10.1210/endo.137.5.8612529
M3 - Article
C2 - 8612529
AN - SCOPUS:0029935071
SN - 0013-7227
VL - 137
SP - 1894
EP - 1903
JO - Endocrinology
JF - Endocrinology
IS - 5
ER -