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Roles of TGF-beta in hepatic fibrosis

Gressner, A. M·2002·Frontiers in Bioscience

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Abstract

TGF-beta has multiple profibrogenic but also anti-inflammatory and immunosuppressive effects. The balance of these actions is required for maintaining tissue homeostasis and an aberrant expression of TGF-beta is involved in a number of disease processes in the liver. In addition to its fibrogenic action leading to transdifferentiation of hepatic stellate cells into myofibroblasts, TGF-beta is also an important negative regulator of proliferation and an inducer of apoptosis. The major portion of TGF-beta is secreted as part of an inactive complex and the details of the activation process in liver have not yet been elucidated. The initially striking simplicity of the core TGF-beta/Smad signaling pathways is rapidly giving way to a much more complex view of intracellular signal transduction mechanisms and recent work has demonstrated the importance of cross-talk among different signaling pathways to either specify, enhance, or inhibit TGF-beta responses. The ubiquitous pathophysiologic relevance of TGF-beta suggests its measurement in blood as a diagnostic tool. Other strategies aim at inhibition of TGF-beta1 function or synthesis as a primary target for the development of antifibrotic strategies and recent advances in cell biology have opened several ways to approach the inhibition of TGF-beta action.

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Involvement of caspase family proteases in transforming growth factor-beta-induced apoptosis.
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Regulation of apoptosis in mouse hepatocytes and alteration of apoptosis by nongenotoxic carcinogens.
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Smad6 functions as an intracellular antagonist of some TGF‐β family members during Xenopus embryogenesis
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Induction of p53 and Bax during TGF-beta 1 initiated apoptosis in rat liver epithelial cells.
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TRANSFORMING GROWTH FACTOR β1 IN RENAL ALLOGRAFT RECIPIENTS1
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Expression and Matrix Deposition of Latent Transforming Growth Factor β Binding Proteins in Normal and Fibrotic Rat Liver and Transdifferentiating Hepatic Stellate Cells in Culture
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The virtuosity of hepatic stellate cells
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Inhibition of Rat Hepatocyte Proliferation by Transforming Growth Factor β and Glucagon Is Associated With Inhibition of Erk2 and P70 S6 Kinase
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Isoforms and splice variant of transforming growth factor β–binding protein in rat hepatic stellate cells
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Expression of isoforms and splice variants of the latent transforming growth factor β binding protein (LTBP) in cultured human liver myofibroblasts
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See all 783

Authors: Gressner, A. M.
Venue: Frontiers in Bioscience
Publisher: IMR Press
Published: 2002
Volume: 7
Issue: 4
Pages: d793-807
ISSN: 1093-4715 (ISSN-L)
1093-9946
DOI: 10.2741/a812
OpenAlex: W1536476892
Cited by: 783
References: 136
FWCI: 12.14
Type: journal article
Language: en
Open access: closed

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Roles of TGF-beta in hepatic fibrosis

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