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Gut. 2018 Oct 8. pii: gutjnl-2018-316906. doi: 10.1136/gutjnl-2018-316906. [Epub ahead of print]

Tight junction proteins in gastrointestinal and liver disease.

Zeisel MB1,2,3, Dhawan P4,5,6, Baumert TF2,3,7.

Author information

1
Inserm U1052, CNRS UMR 5286, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL), Lyon, France.
2
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
3
Université de Strasbourg, Strasbourg, France.
4
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
5
Buffet Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA.
6
VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.
7
Nouvel Hôpital Civil, Pôle Hépato-digestif, Institut Hospitalo-Universitaire, Strasbourg, France.

Abstract

Over the past two decades a growing body of evidence has demonstrated an important role of tight junction (TJ) proteins in the physiology and disease biology of GI and liver disease. On one side, TJ proteins exert their functional role as integral proteins of TJs in forming barriers in the gut and the liver. Furthermore, TJ proteins can also be expressed outside TJs where they play important functional roles in signalling, trafficking and regulation of gene expression. A hallmark of TJ proteins in disease biology is their functional role in epithelial-to-mesenchymal transition. A causative role of TJ proteins has been established in the pathogenesis of colorectal cancer and gastric cancer. Among the best characterised roles of TJ proteins in liver disease biology is their function as cell entry receptors for HCV-one of the most common causes of hepatocellular carcinoma. At the same time TJ proteins are emerging as targets for novel therapeutic approaches for GI and liver disease. Here we review our current knowledge of the role of TJ proteins in the pathogenesis of GI and liver disease biology and discuss their potential as therapeutic targets.

KEYWORDS:

colorectal cancer; hepatitis C; hepatocellular carcinoma; tight junction

PMID:
30297438
PMCID:
PMC6453741
[Available on 2020-04-08]
DOI:
10.1136/gutjnl-2018-316906
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Conflict of interest statement

Competing interests: TFB is a coinventor of a patent/patent application of CLDN1-specific antibodies for prevention and treatment of HCV infection. TFB and MBZ are coinventors of patent applications for anti-claudin 1 monoclonal antibodies for the prevention and treatment of liver disease and HCC.

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