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TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis: Updated

  • Cytokines That Affect Liver Fibrosis and Activation of Hepatic Myofibroblasts (Tatiana Kisseleva, Section Editor)
  • Published:
Current Pathobiology Reports

Abstract

TGF-β is a pro-fibrogenic and antiproliferative protein with multiple functions depending on the cellular context. In liver fibrosis, TGF-β was identified as very robust driver of hepatic stellate cell (HSC) activation and extracellular matrix production, and a plethora of approaches targeting the TGF-β signaling pathway were successfully used to tackle fibrogenesis in animal models of chronic liver diseases. The present review builds on knowledge of the last two decades about TGF-β function in myofibroblast generation and fibrogenesis, and presents the milestone discoveries from the recent 3–5 years. These include findings on downstream targets with fibrogenic function, pathways that facilitate TGF-β expression in HSC, and miRNAs regulated by or regulating the TGF-β pathway. Further, recent data on TGF-β signaling, its integration with other pathways, and TGF-β signaling regulators identified in the setting of fibrotic liver disease are provided. Additionally, we will discuss TGF-β and epithelial-to-mesenchymal transition in liver fibrosis, and what we have learned from other fibrotic diseases, besides liver. Finally, challenges and opportunities for TGF-β-directed therapies in HSC activation, liver fibrosis, and disease progression are discussed.

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Acknowledgments

The authors are grateful for financial support from the BMBF [Virtual Liver network (www.virtual-liver.de), VLN; SD], the EU [IT-Liver consortium (www.it-liver.eu), Marie Curie Training Network; SD, IF, JS], and the DAAD [German Egyptian Research Long-term Scholarship; BD]. Further, we thank Dr. Roman Liebe for final proof of English language.

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Authors and Affiliations

  1. Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer Ufer 1-3, 68167, Mannheim, Germany

    Bedair Dewidar & Steven Dooley

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt

    Bedair Dewidar

  3. Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

    Jitka Soukupova & Isabel Fabregat

  4. Departament de Ciències Fisiològiques II, L’Hospitalet de Llobregat, Universitat de Barcelona, Barcelona, Spain

    Isabel Fabregat

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  1. Bedair Dewidar
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  2. Jitka Soukupova
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  3. Isabel Fabregat
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  4. Steven Dooley
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Correspondence to Steven Dooley.

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This article is part of the Topical Collection on Cytokines That Affect Liver Fibrosis and Activation of Hepatic Myofibroblasts.

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Dewidar, B., Soukupova, J., Fabregat, I. et al. TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis: Updated. Curr Pathobiol Rep 3, 291–305 (2015). https://doi.org/10.1007/s40139-015-0089-8

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