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

作者：Nyabam Samuel; Wang Zhuo; Thibault Thomas; Oluseyi Ayinde; Basar Rameeza; Marshall Lindsay; Griffin Martin

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2016, 1863(9): 2234-2244.

DOI：10.1016/j.bbamcr.2016.05.012

• Tissue transglutaminase
• Cystic fibrosis
• Transforming growth factor beta
• Epithelial-mesenchymal transition
• Cystic fibrosis transmembrane conductance regulator

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 TGF beta 1 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 TGF beta 1 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.

• 出版日期2016-9