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The Transforming Growth Factor-Beta (TGF-β) in Liver Fibrosis

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TGF-β in Human Disease

Abstract

Liver fibrosis is the final consequence of many chronic liver injuries that later develop in cirrhosis and hepatocellular carcinoma (HCC), which are leading causes of morbidity and mortality worldwide. The transforming growth factor-beta (TGF-β) represents a key cytokine that increases in liver in its activated form upon damage and triggers important cellular events during any progression stage of the disease. TGF-β mediates activation of hepatic stellate cells (HSCs) to myofibroblasts and induces cell death and epithelial mesenchymal transition (EMT) of hepatocytes. Both processes may facilitate extracellular matrix (ECM) deposition and scar formation. Regulatory T cells, important negative regulators of inflammation, depend on TGF-β for terminal differentiation, indicating its impact in the inflammatory response. Oxidative stress plays an essential role in mediating liver fibrosis, and recent studies demonstrate that TGF-β contributes to the reactive oxygen species (ROS) production and oxidative damage. Indeed, the active implication of TGF-β signaling in the progression of liver fibrosis makes this cytokine an attractive therapeutic target. In addition to the increasing number of compounds aimed at direct inhibition of the TGF-β pathway, the recent discovery of new downstream molecules with crucial roles in liver fibrosis development, such as NADPH oxidases, is opening the therapeutic perspectives.

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Abbreviations

ALK5:

Activin receptor-like kinase 5

CLD:

Chronic liver disease

ECM:

Extracellular matrix

EMT:

Epithelial mesenchymal transition

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HSCs:

Hepatic stellate cells

NASH:

Non-alcoholic steatohepatitis

NOX:

NADPH oxidase

ROS:

Reactive oxygen species

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Authors and Affiliations

  1. Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain

    Isabel Fabregat

  2. Spanish National Cancer Research Center (CNIO), Madrid, Spain

    Patricia Sancho

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  1. Isabel Fabregat
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  2. Patricia Sancho
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Correspondence to Isabel Fabregat .

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  1. , Dept Medical Biochem Microbiol, Uppsala University, Box 582, Uppsala, SE-751 23, Sweden

    Aristidis Moustakas

  2. , Interdiscip. Grad. Sch. Med. Eng., University of Yamanashi, 1110 Shimokato, Chuo, 409-3898, Yamanashi, Japan

    Keiji Miyazawa

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Fabregat, I., Sancho, P. (2013). The Transforming Growth Factor-Beta (TGF-β) in Liver Fibrosis. In: Moustakas, A., Miyazawa, K. (eds) TGF-β in Human Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54409-8_11

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