ReviewElastin in asthma
Section snippets
Changes to elastin in asthmatic airways
The series of case studies presented by Huber and Koessler in 1922 [34] which described the histology of 21 cases of asthma included several descriptions of elastin with findings ranging from increased, to unchanged, to decreased fibres. In more recent years there have been relatively few studies describing elastin in the airways of patients with asthma, and there is still no consensus in the literature about the alterations. Table 1 describes the recent body of data, showing the great
The role of elastin-degrading proteases in asthma
The role of proteases, particularly matrix metalloproteinases (MMPs), and their inhibitors is currently a key area of research focus in understanding asthma pathophysiology. Recent reviews have thoroughly explored the role of proteases in asthma and potential implications for treatment of MMPs (see [65], [66], [67], [68], [69], [70]) and neutrophil elastase (see [71], [72], [73]), so this paper will not attempt an exhaustive review. However, some key findings relating to elastin degradation are
Biological effects of elastin fragments and new elastin
Elastin fragments are matrikines, which are fragments of ECM with biological activity that are produced upon degradation. The biological effects of degraded elastin on cells support an overall inflammatory and remodelling profile [31], [32], [95], [96]. Some of the effects of elastin are summarised in Table 2. Elastin fragments are identified as chemotactic for monocytes [97], [98] and alveolar macrophages [98] and promote migration of granulocytes [99], suggesting that damage to elastin
Conclusion
Elastin is a structural ECM protein which is expressed in the lung and may play a crucial part in regulating the cellular behaviour in this organ either as a whole protein or fragments thereof. Studies that report on the status of elastin in asthmatic airways, either examining biopsies or tissue obtained from autopsies, reveal changes to elastin ranging between decreased and fragmented fibres [3], [38], [40], [46], [57], increased elastic fibre or bundle content [40], [43], [47], [53], and
Acknowledgements
JKB is supported by a National Health and Medical Research Council, Australia R. Douglas Wright Fellowship #402835. ASW acknowledges support from the Australian Research Council and the National Health & Medical Research Council Australia.
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Elastin in healthy and diseased lung
2022, Current Opinion in BiotechnologyCitation Excerpt :Elastokines correlate with CD4+ T-cell IL-4 production in patients with COPD [23], and specific elastin degradation products are associated with poor prognosis and mortality from this disease [24•], although these correlations are not conclusive evidence of causation. This controversy over correlation versus causation accounts for conflicting findings in studies that point to a contribution by altered elastin to the progression of asthma [25,26]. A large study found increased elastin content in airway walls from patients with severe asthma, but with a possible change in the appearance of elastin, and no changes in collagen or mucins [27].
Matrix metalloproteinases activation in Toxocara canis induced pulmonary pathogenesis
2021, Journal of Microbiology, Immunology and InfectionCitation Excerpt :In normal conditions, fibronectin is a cell adhesive ECM protein highly expressed in developing lungs. During pulmonary pathologies, an increase in fibronectin deposition can cause fibrosis, and to avoid this, MMP-2 and MMP-9 are activated for protein degradation and restructuring of the ECM.36 MMP-2 and MMP-9, can be produced by M2 macrophages, are involved in keratinocyte migration and contribute to lung tissue repair.37,38
Imaging the pulmonary extracellular matrix
2021, Current Opinion in PhysiologyCitation Excerpt :Increased airway wall thickness on HRCT has been reported in asthma, chronic obstructive pulmonary disease (COPD), various interstitial lung diseases [10,12] and is also seen in cigarette smokers with or without COPD [14,46]. In asthma, a thickened airway wall is associated with an increase of ECM components including reticular basement membrane (on HRCT) and ASM mass [11,47]. In COPD, changes observable on CT scanning include emphysema and an increased airway wall thickness.
The Role of Airway Myofibroblasts in Asthma
2019, ChestCitation Excerpt :However, the small airways are also abnormal, with mucus plugging, epithelial damage, extracellular matrix (ECM) deposition, and smooth muscle hyperplasia.14,15 The changes of AR in the large airways include epithelial goblet cell hyperplasia, mucus hypersecretion, increased deposition of ECM, abnormalities of elastin, fibrosis of the subepithelial layer (subepithelial fibrosis) and submucosa, airway smooth muscle (ASM) hyperplasia and/or hypertrophy, angiogenesis, and increased numbers of fibroblasts and myofibroblasts.15-17 Airway remodeling may occur very early in the course of the disease, since subepithelial fibrosis has been detected in infancy.18-21
Mechanics of pulmonary airways: Linking structure to function through constitutive modeling, biochemistry, and histology
2019, Acta BiomaterialiaCitation Excerpt :We are currently investigating such models. The role of GAG and elastin should also be explored; a relative increase in elastin fibers between the trachea and smaller bronchi (Fig. 9) suggests dynamic testing and pentachrome staining would enable measures of the highly deformable elastin structure and visualization of its regional evolution [72]. The unidirectional increasing GAG content distally motivates exploration of viscoelasticity through the incorporation of load-history dependency in constitutive models [12].
Tropoelastin modulates TGF-β1-induced expression of VEGF and CTGF in airway smooth muscle cells
2013, Matrix BiologyCitation Excerpt :Elastogenesis can be restarted to repair damaged elastic fibers although this often results in disorganized elastin (Wagenseil and Mecham, 2007). Elastin is damaged in diseases such as emphysematous chronic obstructive pulmonary disease (COPD) (Shapiro and Ingenito, 2005; Black et al., 2008), cutis laxa (Ringpfeil, 2005; Hu et al., 2006) and asthma (Mauad et al., 1999; Reddel et al., 2012). Disorganized and damaged elastin can contribute to the pathology of disease not only through structural changes (Kelleher et al., 2005) but also molecular effects of exposed elastin sequences (Senior et al., 1980; Fulop et al., 1998; Duca et al., 2004; Turino et al., 2011).