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Experimental models of liver fibrosis

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Abstract

Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

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Abbreviations

ALD:

Alcohol liver disease

α-SMA:

Alpha smooth muscle actin

BDL:

Bile duct ligation

CCl4 :

Carbon tetrachloride

CFSC:

Cirrhotic fat-storing cells

CYP2E1:

Cytochrome P450 2E1

DEN:

Diethylnitrosamine

DMN:

Dimethylnitrosamine

ECM:

Extracellular matrix

GFP:

Green fluorescent protein

GFAP:

Glial fibrillary acidic protein

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HF:

High-fat

HSCs:

Hepatic stellate cells

hTERT:

Human telomerase reverse transcriptase

IL:

Interleukin

LX:

Lieming Xu

MCD:

Methionine-deficient and choline-deficient

Mdr2:

Multidrug resistance-associated protein 2

MMPs:

Matrix metalloproteinases

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

NFSC:

Normal fat-storing cells

PCLS:

Precision-cut liver slices

PDGF:

Platelet-derived growth factor

ROS:

Reactive oxygen species

TIMPs:

Tissue inhibitors metalloproteinases

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

TSV40:

Large T-antigen of simian virus 40

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Acknowledgments

This work was financially supported by the grants of the University Hospital of the Vrije Universiteit Brussel, Belgium (Willy Gepts Fonds UZ-VUB), the Fund for Scientific Research, Flanders (FWO grants G009514N and G010214N), the European Research Council (ERC Starting Grant 335476), the University of São Paulo, Brazil (USP), and the Foundation for Research Support of the State of São Paulo (FAPESP SPEC Grant 2013/50420-6).

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    Authors and Affiliations

    1. Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium

      Sara Crespo Yanguas, Joost Willebrords, Michaël Maes & Mathieu Vinken

    2. Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

      Bruno Cogliati

    3. Department of Hepato-Gastroenterology, Algemeen Stedelijk Ziekenhuis, Aalst, Belgium

      Isabelle Colle

    4. Department of Abdominal Surgery and Hepato-Pancreatico-Biliary Surgery, Algemeen Stedelijk Ziekenhuis, Aalst, Belgium

      Bert van den Bossche

    5. Department of Gastroenterology, Clinical Division, Hepatology Branch, University of São Paulo School of Medicine, São Paulo, Brazil

      Claudia Pinto Marques Souza de Oliveira

    6. Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil

      Wellington Andraus

    7. Laboratory of Medical Investigation, Department of Pathology, University of São Paulo School of Medicine, São Paulo, Brazil

      Venâncio Avancini Alves

    8. Laboratoire d’Hépato-Gastro-Entérologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium

      Isabelle Leclercq

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    1. Sara Crespo Yanguas
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    Correspondence to Mathieu Vinken.

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    Sara Crespo Yanguas and Bruno Cogliati have contributed equally to this paper.

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    Crespo Yanguas, S., Cogliati, B., Willebrords, J. et al. Experimental models of liver fibrosis. Arch Toxicol 90, 1025–1048 (2016). https://doi.org/10.1007/s00204-015-1543-4

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    • DOI: https://doi.org/10.1007/s00204-015-1543-4

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