title: Does aberrant activation of the epithelial-mesenchymal trophic unit play a key role in asthma or is it an unimportant sideshow?
abstract: Mechanisms underlying the pathogenesis of asthma remain elusive, although the pathological changes observed in human lungs at autopsy are consistent with those of a well-defined chronic inflammatory process and are related to disease severity. Areas of epithelial metaplasia and damage, and thickening of the sub-epithelial basal lamina, are common findings. Epithelial cell proliferation is accompanied by a concomitant increase in the proliferation of sub-epithelial fibroblasts. Each of these processes can be upregulated by cytokines and growth factors released from undamaged neighboring cells. However, there is mounting evidence to suggest that aberrant repair signals present in chronically inflamed airways may influence epithelial cell proliferation and regeneration. Furthermore, an aberrant repair process occurring at the mucosal surface might trigger a cascade of events deeper within the sub-mucosa, leading to direct effects on the number and behaviour of mesenchymal cells, and the resultant increased deposition of extracellular matrix that contributes to airway wall remodeling. These data have led an increasing number of investigators to ask the question whether the epithelial-mesenchymal trophic unit, central to lung development, becomes "re-activated" in asthma.
authors.affiliation: Asthma & Allergy Research Institute and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, 35 Stirling Highway, Crawley, Western Australia, 6009 Australia. dknight@aari.uwa.edu.au
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Knight
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Lane
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Stick
mesh_terms: D001249:Asthma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008168:Lung / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology; D008648:Mesoderm / Q000276:immunology / Q000378:metabolism / Q000473:pathology*