Signalling by Wnt/beta[Greek letter]-catenin in human bronchial epithelial cells
Signalling by Wnt/beta[Greek letter]-catenin in human bronchial epithelial cells
To investigate the role of Wnt signal transduction in the airways, I characterised the expression of key pathway components in human bronchial epithelial (HBE) cells and studied the influence of cell density on pathway activity, using subconfluent cells in log-phase growth as a simple model of repairing epithelium. Primary HBE cells and H292 bronchial epithelial cells were found to express TCF-4 and -3, with variable low-level expression of TCF-1 and LEF-1, transcription factors that are regulated by β-catenin. The cells also had the potential to respond to Wnt signals through expression of members of the Frizzled receptor family, including FZD-5 and -6. In confluent H292 cells, 20mM lithium and 25% v/v Wnt-3a conditioned medium induced 4.5-fold (p=0.008) and 1.4-fold (p=0.006) increases in TOPflash activity, respectively. Under conditions of reduced cell density, TOPflash activity increased 1.8-fold (p=0.002) in association with increased nuclear localisation of hypophosphorylated (transcriptionally active) β-catenin and increased cell proliferation. This up-regulation in reporter activity occurred independently of EGF receptor activation and could not be recapitulated by use of low-calcium medium to disrupt cadherin-mediated cell-cell adhesion, but was associated with changes in FZD6 gene expression. I conclude that reactivation of this embryonic pathway might play a role in bronchial epithelial regeneration, and that modulation of Fzd6 receptors may regulate Wnt signalling at confluence. Recognising that chronic inflammatory disorders of the airways involve epithelial damage and repair, I speculate that altered Wnt signalling might contribute to disease pathogenesis or progression.
University of Southampton
Steel, Mark Dominic
1afd7790-db8c-43d0-8a0a-02acfc0f5a33
2006
Steel, Mark Dominic
1afd7790-db8c-43d0-8a0a-02acfc0f5a33
Steel, Mark Dominic
(2006)
Signalling by Wnt/beta[Greek letter]-catenin in human bronchial epithelial cells.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
To investigate the role of Wnt signal transduction in the airways, I characterised the expression of key pathway components in human bronchial epithelial (HBE) cells and studied the influence of cell density on pathway activity, using subconfluent cells in log-phase growth as a simple model of repairing epithelium. Primary HBE cells and H292 bronchial epithelial cells were found to express TCF-4 and -3, with variable low-level expression of TCF-1 and LEF-1, transcription factors that are regulated by β-catenin. The cells also had the potential to respond to Wnt signals through expression of members of the Frizzled receptor family, including FZD-5 and -6. In confluent H292 cells, 20mM lithium and 25% v/v Wnt-3a conditioned medium induced 4.5-fold (p=0.008) and 1.4-fold (p=0.006) increases in TOPflash activity, respectively. Under conditions of reduced cell density, TOPflash activity increased 1.8-fold (p=0.002) in association with increased nuclear localisation of hypophosphorylated (transcriptionally active) β-catenin and increased cell proliferation. This up-regulation in reporter activity occurred independently of EGF receptor activation and could not be recapitulated by use of low-calcium medium to disrupt cadherin-mediated cell-cell adhesion, but was associated with changes in FZD6 gene expression. I conclude that reactivation of this embryonic pathway might play a role in bronchial epithelial regeneration, and that modulation of Fzd6 receptors may regulate Wnt signalling at confluence. Recognising that chronic inflammatory disorders of the airways involve epithelial damage and repair, I speculate that altered Wnt signalling might contribute to disease pathogenesis or progression.
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Published date: 2006
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Local EPrints ID: 466078
URI: http://eprints.soton.ac.uk/id/eprint/466078
PURE UUID: 6486b2f6-4f27-4dc2-984e-ba2a94aeeb9c
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Date deposited: 05 Jul 2022 04:15
Last modified: 16 Mar 2024 20:30
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Author:
Mark Dominic Steel
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