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Myd88 deficiency influences murine tracheal epithelial metaplasia and submucosal gland abundance

Giangreco, A; Lu, LW; Mazzatti, DJ; Spencer-Dene, B; Nye, E; Teixeira, VH; Janes, SM; (2011) Myd88 deficiency influences murine tracheal epithelial metaplasia and submucosal gland abundance. J PATHOL , 224 (2) 190 - 202. 10.1002/path.2876.

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Abstract

Tracheal epithelial remodelling, excess mucus production, and submucosal gland hyperplasia are features of numerous lung diseases, yet their origins remain poorly understood. Previous studies have suggested that NF-kappa B signalling may regulate airway epithelial homeostasis. The purpose of this study was to determine whether deletion of the NF-kappa B signalling pathway protein myeloid differentiation factor 88 (Myd88) influenced tracheal epithelial cell phenotype. We compared wild-type and Myd88-deficient or pharmacologically inhibited adult mouse tracheas and determined that in vivo Myd88 deletion resulted in increased submucosal gland number, secretory cell metaplasia, and excess mucus cell abundance. We also found that Myd88 was required for normal resolution after acute tracheal epithelial injury. Microarray analysis revealed that uninjured Myd88-deficient tracheas contained 103 transcripts that were differentially expressed relative to wild-type and all injured whole tracheal samples. These clustered into several ontologies and networks that are known to functionally influence epithelial cell phenotype. Comparing these transcripts to those expressed in airway progenitor cells revealed only five common genes, suggesting that Myd88 influences tracheal epithelial homeostasis through an extrinsic mechanism. Overall, this study represents the first identification of Myd88 as a regulator of adult tracheal epithelial cell phenotype. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Type: Article
Title: Myd88 deficiency influences murine tracheal epithelial metaplasia and submucosal gland abundance
DOI: 10.1002/path.2876
Keywords: Myd88, mucus, trachea, secretion, injury, homeostasis, FACTOR-KAPPA-B, LIPOPOLYSACCHARIDE-BINDING PROTEIN, MYD88-DEFICIENT DENDRITIC CELLS, AIRWAY EPITHELIUM, STEM-CELLS, ECTODERMAL DYSPLASIA, MOUSE, DIFFERENTIATION, INFLAMMATION, ACTIVATION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/1307820
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