A novel regulatory role for tissue transglutaminase in epithelial-mesenchymal transition in cystic fibrosis


Cystic fibrosis (CF) is a genetic disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) for which there is no overall effective treatment. Recent work indicates tissue transglutaminase (TG2) plays a pivotal intracellular role in proteostasis in CF epithelia and that the pan TG inhibitor cysteamine improves CFTR stability. Here we show TG2 has another role in CF pathology linked with TGFβ1 activation and signalling, induction of epithelial-mesenchymal transition (EMT), CFTR stability and induction of matrix deposition. We show that increased TG2 expression in normal and CF bronchial epithelial cells increases TGFβ1 levels, promoting EMT progression, and impairs tight junctions as measured by Transepithelial Electric Resistance (TEER) which can be reversed by selective inhibition of TG2 with an observed increase in CFTR stability. Our data indicate that selective inhibition of TG2 provides a potential therapeutic avenue for reducing fibrosis and increasing CFTR stability in CF.

Publication DOI: https://doi.org/10.1016/j.bbamcr.2016.05.012
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: tissue transglutaminase,cystic fibrosis,transforming growth factor β,epithelial-mesenchymal transition,cystic fibrosis transmembrane conductance regulator,Cell Biology,Molecular Biology
Publication ISSN: 0167-4889
Last Modified: 27 Jun 2024 08:50
Date Deposited: 31 May 2016 15:59
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2016-09
Published Online Date: 2016-05-24
Accepted Date: 2016-05-17
Submitted Date: 2015-12-05
Authors: Nyabam, Samuel
Wang, Zhuo (ORCID Profile 0000-0002-2212-8318)
Thibault, Thomas
Ayinde, Oluseyi
Basar, Rameeza
Marshall, Lindsay (ORCID Profile 0000-0001-7281-7974)
Griffin, Martin (ORCID Profile 0000-0003-3824-306X)

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