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

Samuel Nyabam, Zhuo Wang, Thomas Thibault, Oluseyi Ayinde, Rameeza Basar, Lindsay Marshall, Martin Griffin

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish
Pages2234-2244
Number of pages11
JournalBBA - Molecular Cell Research
Volume1863
Issue number9
Early online date24 May 2016
DOIs
Publication statusPublished - Sep 2016

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Epithelial-Mesenchymal Transition
Cystic Fibrosis
Cysteamine
Inborn Genetic Diseases
Tight Junctions
Electric Impedance
Fibrosis
Epithelium
Epithelial Cells
transglutaminase 2
Pathology
Mutation

Bibliographical note

© 2016, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • tissue transglutaminase
  • cystic fibrosis
  • transforming growth factor β
  • epithelial-mesenchymal transition
  • cystic fibrosis transmembrane conductance regulator

Cite this

Nyabam, Samuel ; Wang, Zhuo ; Thibault, Thomas ; Ayinde, Oluseyi ; Basar, Rameeza ; Marshall, Lindsay ; Griffin, Martin. / A novel regulatory role for tissue transglutaminase in epithelial-mesenchymal transition in cystic fibrosis. In: BBA - Molecular Cell Research. 2016 ; Vol. 1863, No. 9. pp. 2234-2244.
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A novel regulatory role for tissue transglutaminase in epithelial-mesenchymal transition in cystic fibrosis. / Nyabam, Samuel; Wang, Zhuo; Thibault, Thomas; Ayinde, Oluseyi; Basar, Rameeza; Marshall, Lindsay; Griffin, Martin.

In: BBA - Molecular Cell Research, Vol. 1863, No. 9, 09.2016, p. 2234-2244.

Research output: Contribution to journalArticle

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AU - Marshall, Lindsay

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