title: Myd88 deficiency influences murine tracheal epithelial metaplasia and submucosal gland abundance.
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-κB signalling may regulate airway epithelial homeostasis. The purpose of this study was to determine whether deletion of the NF-κB 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.
authors.affiliation: Centre for Respiratory Research, University College London, Rayne Institute, 5 University Street, London WC1E 6JF, UK. a.giangreco@ucl.ac.uk
authors.forename: Adam
authors.initials: A
authors.lastname: Giangreco
authors.forename: Liwen
authors.initials: L
authors.lastname: Lu
authors.forename: Dawn J
authors.initials: DJ
authors.lastname: Mazzatti
authors.forename: Bradley
authors.initials: B
authors.lastname: Spencer-Dene
authors.forename: Emma
authors.initials: E
authors.lastname: Nye
authors.forename: Vitor Hugo
authors.initials: VH
authors.lastname: Teixeira
authors.forename: Sam M
authors.initials: SM
authors.lastname: Janes
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000502:physiology; D020545:Respiratory Mucosa / Q000293:injuries / Q000473:pathology; D014132:Trachea / Q000293:injuries / Q000473:pathology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D053594:Myeloid Differentiation Factor 88