Polymorphisms of the <i>ADAM33</i> gene are associated with accelerated lung function decline in asthma

Jongepier, Hajo; Boezen, H. Marike; Dijkstra, Ate; Howard, Timothy D.; Vonk, Judith M.; Koppelman, Gerard H.; Zheng, S. Lilly; Meyers, Deborah A.; Bleecker, Eugene R.; Postma, Dirkje S.

doi:10.1111/j.1365-2222.2004.1938.x

Cited by 187 publications

(120 citation statements)

References 8 publications

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“…In this context, it is noteworthy that ADAM33 is selectively expressed in mesenchymal cells [76], strongly implicating it in airway remodelling. Consistent with this proposal, a rare allele of the S_2 polymorphism of ADAM33 is significantly associated with excessive decline in FEV1 in asthmatic subjects [82] and chronic obstructive pulmonary disease patients [83]. Furthermore, in a prospective birth cohort study, polymorphisms in ADAM33 predict impaired early-life lung function [84].…”

Section: Increased Deposition Of Extracellular Matrixsupporting

confidence: 61%

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Boxall

Holgate²,

Davies³

2006

Eur Respir J

226

187

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Asthma is increasing in prevalence in the developing world, affecting ,10% of the world's population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time.Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-b is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma.This review highlights the role of transforming growth factor-b in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo, however, it is the balance between transforming growth factor-b and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways.A fuller comprehension of the actions of transforming growth factor-b, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.

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Section: Increased Deposition Of Extracellular Matrixsupporting

confidence: 61%

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Boxall

Holgate²,

Davies³

2006

Eur Respir J

226

187

View full text Add to dashboard Cite

show abstract

“…In recent studies, ADAMs have been suggested to play a role in a pulmonary disease like asthma [5][6][7][8][9] but also in interstitial lung disease [10], eosinophilic pneumonia [11], and lung cancer [12]. Moreover, single nucleotide polymorphisms (SNPs) in ADAM33 have been found to be associated with asthma development and progression [7] as well as with progressive lung function loss in the general population and development of COPD [13,14]. In view of the association of ADAMs with respiratory diseases, our study was undertaken to assess the expression and localization of various ADAMs with metalloproteinase activity (ADAM8, ADAM9, AD-AM10, ADAM17, ADAM19, and ADAM33) in human lung tissue.…”

Section: Introductionmentioning

confidence: 99%

Expression of ADAMs (“a disintegrin and metalloprotease”) in the human lung

et al. 2009

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In view of the associations of "a disintegrin and metalloprotease" (ADAM) with respiratory diseases, we assessed the expression of various ADAMs in human lung tissue. Lung tissue was obtained from nine individuals who underwent surgery for lung cancer or underwent lung transplantation for emphysema. Also, 16HBE 14o-(human bronchial epithelial) and A549 (alveolar type II epitheliumlike) cell lines were used. Immunohistochemistry was performed with antibodies recognizing different ADAM domains. The ADAMs were typically distributed over the bronchial epithelium. ADAM8 and ADAM10 were expressed diffusely in all layers of the epithelium. ADAM9, ADAM17, and ADAM19 were predominantly expressed in the apical part of the epithelium, and ADAM33 was predominantly and strongly expressed in basal epithelial cells. In smooth muscle, ADAM19 and ADAM17 were strongly expressed, as was ADAM33, though this expression was weaker. ADAM33 was strongly expressed in vascular endothelium. All ADAMs were generally expressed in inflammatory cells. The typical distribution of ADAMs in the lung, especially in the epithelium, is interesting and suggests a localized function. As most ADAMs are involved in release of (pro-) inflammatory mediators and growth factors, they may play an important role in the first line of defense and in initiation of repair events in the airways.

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“…54 Polymorphisms in ADAM33 are associated with a more rapid annual decline in postbronchodilator forced expiratory volume in one second (FEV1). 55 Such genetic associations may explain why severity and outcomes in adult asthma can to a certain extent be predicted in childhood and do not necessarily relate to inflammatory biomarkers. 56 Increased ASM numbers seem to be the cause rather than the consequence of severe disease in asthma.…”

Section: Restoration Of N Ormal Airway Structure (Mod Elling)mentioning

confidence: 99%

Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited

Samitas

Carter

Kariyawasam

et al. 2017

Allergy

210

156

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Allergic rhinitis (AR), chronic rhinosinusitis (CRS) and asthma often co-exist. The one airway model proposes that disease mechanisms occurring in the upper airway may mirror lower airway events. Airway remodelling is the term used to describe tissue structural changes that occur in a disease setting and reflect the dynamic process of tissue restructuring during wound repair. Remodelling has been long identified in the lower airways in asthma and is characterized by epithelial shedding, goblet cell hyperplasia, basement membrane thickening, subepithelial fibrosis, airway smooth muscle hyperplasia and increased angiogenesis. The concept of upper airway remodelling has only recently been introduced, and data so far are limited and often conflicting, an indication that more detailed studies are needed. Whilst remodelling changes in AR are limited, CRS phenotypes demonstrate epithelial hyperplasia, increased matrix deposition and degradation along with accumulation of plasma proteins. Despite extensive research over the past years, the precise cellular and molecular mechanisms involved in airway remodelling remain incompletely defined. This review describes our current rather limited understanding of airway remodelling processes in AR, CRS and asthma and presents mechanisms both shared and distinct between the upper and lower airways. Delineation of shared and disease-specific pathogenic mechanisms of remodelling between the sinonasal system and the lung may guide the rational design of more effective therapeutic strategies targeting upper and lower airways concomitantly and improving the health of individuals with inflammatory airway diseases.

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Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma

Abstract: These findings suggest that a variant in ADAM33 is not only important in the development of asthma but also in disease progression, possibly related to enhanced airway remodelling.

Cited by 187 publications

References 8 publications

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma

Expression of ADAMs (“a disintegrin and metalloprotease”) in the human lung

Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited

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