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Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation (2023)
Journal Article
Goodwin, A. T., John, A. E., Joseph, C., Habgood, A., Tatler, A. L., Susztak, K., …Jenkins, R. G. (2023). Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation. Development, 150(9), https://doi.org/10.1242/dev.201046

Alveolar development and repair require tight spatiotemporal regulation of numerous signalling pathways that are influenced by chemical and mechanical stimuli. Mesenchymal cells play key roles in numerous developmental processes. Transforming growth... Read More about Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation.

Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia (2023)
Journal Article
Calthorpe, R. J., Poulter, C., Smyth, A. R., Sharkey, D., Bhatt, J., Jenkins, G., & Tatler, A. L. (2023). Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia. AJP - Lung Cellular and Molecular Physiology, 324(3), L285-L296. https://doi.org/10.1152/ajplung.00106.2021

As survival of extremely preterm infants continues to improve, there is also an associated increase in bronchopulmonary dysplasia (BPD), one of the most significant complications of preterm birth. BPD development is multifactorial resulting from expo... Read More about Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia.

Differential remodelling in small and large murine airways revealed by novel whole lung airway analysis (2023)
Journal Article
Tatler, A. L., Philp, C. J., Hill, M. R., Cox, S., Bullock, A. M., John, A., …Brook, B. S. (2023). Differential remodelling in small and large murine airways revealed by novel whole lung airway analysis. American Journal of Physiology-Lung Cellular and Molecular Physiology, 324(3), L271-L284. https://doi.org/10.1152/ajplung.00034.2022

Airway remodelling occurs in chronic asthma leading to increased airway smooth muscle (ASM) mass and extra-cellular matrix (ECM) deposition. Whilst extensively studied in murine airways, studies report only selected larger airways at one time point m... Read More about Differential remodelling in small and large murine airways revealed by novel whole lung airway analysis.

Plasma cells: a feasible therapeutic target in pulmonary fibrosis? (2022)
Journal Article
Goodwin, A. T., Noble, P. W., & Tatler, A. L. (2022). Plasma cells: a feasible therapeutic target in pulmonary fibrosis?. European Respiratory Journal, 60(5), Article 2201748. https://doi.org/10.1183/13993003.01748-2022

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterised by the irreversible replacement of normal lung parenchyma with stiff scar tissue. The prognosis of IPF is very poor, with a median survival worse than many canc... Read More about Plasma cells: a feasible therapeutic target in pulmonary fibrosis?.

Lysyl oxidase like 2 is increased in asthma and contributes to asthmatic airway remodelling (2022)
Journal Article
Ramis, J., Middlewick, R., Pappalardo, F., Cairns, J. T., Stewart, I. D., John, A. E., …Tatler, A. L. (2022). Lysyl oxidase like 2 is increased in asthma and contributes to asthmatic airway remodelling. European Respiratory Journal, 60(1), Article 2004361. https://doi.org/10.1183/13993003.04361-2020

BACKGROUND: Airway smooth muscle (ASM) cells are fundamental to asthma pathogenesis, influencing bronchoconstriction, airway hyperresponsiveness and airway remodelling. The extracellular matrix (ECM) can influence tissue remodelling pathways; however... Read More about Lysyl oxidase like 2 is increased in asthma and contributes to asthmatic airway remodelling.

COVID‐19 and pulmonary fibrosis: A potential role for lung epithelial cells and fibroblasts (2021)
Journal Article
John, A. E., Joseph, C., Jenkins, G., & Tatler, A. L. (2021). COVID‐19 and pulmonary fibrosis: A potential role for lung epithelial cells and fibroblasts. Immunological Reviews, 302(1), 228-240. https://doi.org/10.1111/imr.12977

The COVID-19 pandemic rapidly spread around the world following the first reports in Wuhan City, China in late 2019. The disease, caused by the novel SARS-CoV-2 virus, is primarily a respiratory condition that can affect numerous other bodily systems... Read More about COVID‐19 and pulmonary fibrosis: A potential role for lung epithelial cells and fibroblasts.

Reduced biomechanical models for precision-cut lung-slice stretching experiments (2021)
Journal Article
Pybus, H. J., Tatler, A. L., Edgar, L. T., O’Dea, R. D., & Brook, B. S. (2021). Reduced biomechanical models for precision-cut lung-slice stretching experiments. Journal of Mathematical Biology, 82(5), Article 35. https://doi.org/10.1007/s00285-021-01578-2

Precision-cut lung-slices (PCLS), in which viable airways embedded within lung parenchyma are stretched or induced to contract, are a widely used ex vivo assay to investigate bronchoconstriction and, more recently, mechanical activation of proremodel... Read More about Reduced biomechanical models for precision-cut lung-slice stretching experiments.

Loss of ELK1 has differential effects on age-dependent organ fibrosis and integrin expression (2019)
Journal Article
Cairns, J. T., Habgood, A., Edwards-Pritchard, R. C., Wilkinson, C., Stewart, I. D., Leslie, J., …Tatler, A. L. (2020). Loss of ELK1 has differential effects on age-dependent organ fibrosis and integrin expression. International Journal of Biochemistry and Cell Biology, 120, Article 105668. https://doi.org/10.1016/j.biocel.2019.105668

ETS domain-containing protein-1 (ELK1) is a transcription factor important in regulating ?v?6 integrin expression. ?v?6 integrins activate the profibrotic cytokine Transforming Growth Factor ?1 (TGF?1) and are increased in the alveolar epithelium in... Read More about Loss of ELK1 has differential effects on age-dependent organ fibrosis and integrin expression.

Loss of ELK1 has differential effects on age-dependent organ fibrosis (2019)
Journal Article
Cairns, J. T., Habgood, A., Edwards-Pritchard, R. C., Joseph, C., John, A. E., Wilkinson, C., …Tatler, A. L. (2020). Loss of ELK1 has differential effects on age-dependent organ fibrosis. International Journal of Biochemistry and Cell Biology, 120, Article 105668. https://doi.org/10.1016/j.biocel.2019.105668

© 2019 The Author(s) ETS domain-containing protein-1 (ELK1) is a transcription factor important in regulating αvβ6 integrin expression. αvβ6 integrins activate the profibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and are increased in the al... Read More about Loss of ELK1 has differential effects on age-dependent organ fibrosis.

PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy (2018)
Journal Article
Osman, G., Rodriguez, J., Chan, S. Y., Chisholm, J., Duncan, G., Kim, N., …Dixon, J. E. (2018). PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy. Journal of Controlled Release, 285, 35-45. https://doi.org/10.1016/j.jconrel.2018.07.001

The lung remains an attractive target for the gene therapy of monogenetic diseases such as cystic fibrosis (CF). Despite over 27 clinical trials, there are still very few gene therapy vectors that have shown any improvement in lung function; highligh... Read More about PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy.

A theoretical model of inflammation- and mechanotransduction-driven asthmatic airway remodelling (2018)
Journal Article
Hill, M., Philp, C. J., Billington, C. K., Tatler, A. L., Johnson, S. R., O'Dea, R. D., & Brook, B. S. (2018). A theoretical model of inflammation- and mechanotransduction-driven asthmatic airway remodelling. Biomechanics and Modeling in Mechanobiology, 17(5), 1451-1470. https://doi.org/10.1007/s10237-018-1037-4

© 2018, The Author(s). Inflammation, airway hyper-responsiveness and airway remodelling are well-established hallmarks of asthma, but their inter-relationships remain elusive. In order to obtain a better understanding of their inter-dependence, we de... Read More about A theoretical model of inflammation- and mechanotransduction-driven asthmatic airway remodelling.

Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema (2016)
Journal Article
John, A. E., Wilson, M. R., Habgood, A., Porte, J., Tatler, A. L., Stavrou, A., …Jenkins, R. G. (2016). Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema. Science Signaling, 9(451), Article ra104. https://doi.org/10.1126/scisignal.aad5568

Heterotrimeric guanine nucleotide–binding protein (G protein) signaling is a ubiquitous signaling system that links hundreds of G protein–coupled receptors (GPCRs) with four G protein signaling pathways. Two of these pathways, one mediated by Gq and... Read More about Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema.

Amplification of TGF? Induced ITGB6 Gene Transcription May Promote Pulmonary Fibrosis (2016)
Journal Article
Porte, J., Tatler, A. L., Jenkins, G., Goodwin, A. T., Clifford, R., Gbolahan, O., …Kolb, M. (2016). Amplification of TGFβ Induced ITGB6 Gene Transcription May Promote Pulmonary Fibrosis. PLoS ONE, 11(8), 1-19. https://doi.org/10.1371/journal.pone.0158047

© 2016 Tatler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are cre... Read More about Amplification of TGF? Induced ITGB6 Gene Transcription May Promote Pulmonary Fibrosis.

Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis (2016)
Journal Article
Habgood, A., Tatler, A. L., Porte, J., Wahl, S. M., Laurent, G. J., John, A. E., …Jenkins, G. (in press). Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis. Laboratory Investigation, https://doi.org/10.1038/labinvest.2016.40

Idiopathic pulmonary fibrosis is a progressive, fatal disease with limited treatment options. Protease-mediated transforming growth factor-? (TGF-?) activation has been proposed as a pathogenic mechanism of lung fibrosis. Protease activity in the lun... Read More about Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis.

Caffeine inhibits TGF? activation in epithelial cells, interrupts fibroblast responses to TGF?, and reduces established fibrosis in ex vivo precision-cut lung slices (2016)
Journal Article
Tatler, A. L., Barnes, J., Habgood, A., Goodwin, A., McAnulty, R., & Jenkins, G. (2016). Caffeine inhibits TGF? activation in epithelial cells, interrupts fibroblast responses to TGF?, and reduces established fibrosis in ex vivo precision-cut lung slices. Thorax, 71(6), 565-567. https://doi.org/10.1136/thoraxjnl-2015-208215

Caffeine is a commonly used food additive found naturally in many products. In addition to potently stimulating the central nervous system caffeine is able to affect various systems within the body including the cardiovascular and respiratory systems... Read More about Caffeine inhibits TGF? activation in epithelial cells, interrupts fibroblast responses to TGF?, and reduces established fibrosis in ex vivo precision-cut lung slices.

Reduced Ets domain-containing protein Elk1 promotes pulmonary fibrosis via increased integrin ?v?6 expression (2016)
Journal Article
Tatler, A. L., Habgood, A., Porte, J., John, A. E., Stavrou, A., Hodge, E., …Jenkins, G. (2016). Reduced Ets domain-containing protein Elk1 promotes pulmonary fibrosis via increased integrin αvβ6 expression. Journal of Biological Chemistry, 291(18), 9540-9553. https://doi.org/10.1074/jbc.M115.692368

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with high mortality. Active TGF?1 is considered central to the pathogenesis of IPF. A major mechanism of TGF?1 activation in the lung involves the epithelially restricted ?v?6... Read More about Reduced Ets domain-containing protein Elk1 promotes pulmonary fibrosis via increased integrin ?v?6 expression.

Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma (2015)
Journal Article
Lilburn, D. M., Tatler, A. L., Six, J. S., Lesbats, C., Habgood, A., Porte, J., …Meersmann, T. (2015). Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma. Magnetic Resonance in Medicine, 76(4), 1224-1235. https://doi.org/10.1002/mrm.26003

© 2015 The Authors. Wiley Periodicals, Inc. Purpose: Asthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independen... Read More about Investigating lung responses with functional hyperpolarized xenon-129 MRI in an ex vivo rat model of asthma.

CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: Regulation by BET (2015)
Journal Article
Clifford, R. L., Patel, J. K., John, A. E., Tatler, A. L., Mazengarb, L., Brightling, C. E., & Knox, A. J. (2015). CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: Regulation by BET. AJP - Lung Cellular and Molecular Physiology, 308(9), L962-L972. https://doi.org/10.1152/ajplung.00021.2015

© 2015 The American Physiological Society. Asthma is characterized by airway inflammation and remodeling and CXCL8 is a CXC chemokine that drives steroid-resistant neutrophilic airway inflammation. We have shown that airway smooth muscle (ASM) cells... Read More about CXCL8 histone H3 acetylation is dysfunctional in airway smooth muscle in asthma: Regulation by BET.