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Tight junction proteins in gastrointestinal and liver disease
  1. Mirjam B Zeisel1,2,3,
  2. Punita Dhawan4,5,6,
  3. Thomas F Baumert2,3,7
  1. 1 Inserm U1052, CNRS UMR 5286, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL), Lyon, France
  2. 2 Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France
  3. 3 Université de Strasbourg, Strasbourg, France
  4. 4 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
  5. 5 Buffet Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA
  6. 6 VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
  7. 7 Nouvel Hôpital Civil, Pôle Hépato-digestif, Institut Hospitalo-Universitaire, Strasbourg, France
  1. Correspondence to Dr Mirjam B Zeisel, Inserm U1052, CNRS UMR 5286, Cancer Research Center of Lyon (CRCL), Université de Lyon (UCBL), Lyon 69424, France; mirjam.zeisel{at}inserm.fr, Dr Punita Dhawan, University of Nebraska for Medical Sciences, 985870 Nebraska Medical Center, Omaha, NE 68198-5870 ; punita.dhawan{at}unmc.edu and Dr Thomas F Baumert, Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 3 rue Koeberlé, 67000 Strasbourg, France ; thomas.baumert{at}unistra.fr

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.

  • hepatitis C
  • hepatocellular carcinoma
  • colorectal cancer
  • tight junction

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Footnotes

  • Contributors MBZ, PD and TFB wrote the manuscript.

  • Funding The authors’ work is supported by ARC, Paris and Institut Hospitalo-Universitaire, Strasbourg (TheraHCC IHUARC IHU201301187), the European Union (ERC-AdG-HEPCIR, ERC-PoC-2016-PRELICAN, EU H2020-667273-HEPCAR, U Strasbourg Foundation HEPKIN), the National Institutes of Health (NCI 1R21CA209940-01A1, NIAID R03AI131066, NIAID 5U19AI123862-02), the Institut Universitaire de France (IUF), the IdEx Program of the University of Strasbourg, the Impulsion Program of the IDEXLYON, BX002086 (VA merit), CA216746 (NIH/NCI) and a pilot project award from Fred and Pamela Buffet Cancer Center, which is funded by a National Cancer Institute Cancer Center Support Grant under award number P30 CA036727. This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and benefits from funding from the state managed by the French National Research Agency as part of the investments for the future programme.

  • 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.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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