Correlation between airway responsiveness and proteoglycan production by bronchial fibroblasts from normal and asthmatic subjects

Westergren‐Thorsson, Gunilla; Chakir, Jamila; Lafrenière-Allard, Marie Josée; Boulet, Louis Philippe; Tremblay, Guy M.

doi:10.1016/s1357-2725(02)00058-4

Cited by 87 publications

(83 citation statements)

References 33 publications

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“…Previous attempts to characterize phenotypes of airway fibroblasts in asthma (and other diseases) have compared "diseased state" with normal airway fibroblasts (27)(28)(29)(30). In asthma, these studies have yielded conflicting results.…”

Section: Discussionmentioning

confidence: 99%

Regional Fibroblast Heterogeneity in the Lung

Kotaru

Schoonover²,

Trudeau³

et al. 2006

Am J Respir Crit Care Med

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Rationale: Excessive deposition of extracellular matrix occurs in proximal airways of individuals with asthma, but fibrosis in distal lung has not been observed. Whether differing fibrotic capacities of fibroblasts from these two regions contribute to this variability is unknown. Objectives: We compared morphologic and functional characteristics of fibroblasts isolated from proximal airways and distal lung parenchyma to determine phenotypic differences. Methods: Concurrent proximal airway and distal lung biopsies were obtained by bronchoscopy from subjects with asthma to isolate airway and distal lung fibroblasts, respectively. The following characteristics were compared: morphology, proliferation, ␣-smooth muscle actin expression, and synthesis of procollagen type I and eotaxin-1. Results: Airway fibroblasts (AFs) are morphologically distinct from distal lung fibroblasts (DLFs): they are larger (2.3-fold greater surface area vs. matched DLFs; p ϭ 0.02), stellate in appearance, and with more cytoplasmic projections compared with the spindleshaped DLFs. AFs synthesized more procollagen type I than did DLFs at baseline (twofold higher; p ϭ 0.003) and after transforming growth factor-␤ stimulation (1.4-fold higher; p ϭ 0.02). Similarly, AFs produced more eotaxin-1 than did DLFs at baseline (2.5-fold higher; p ϭ 0.004) and after interleukin-13 stimulation (13-fold higher; p ϭ 0.0001). In contrast, DLFs proliferate more than AFs with serum stimulation (about sixfold greater; p ϭ 0.03). Unstimulated DLFs also expressed more ␣-smooth muscle actin than did corresponding AFs (p ϭ 0.006). Conclusions: These studies suggest that at least two phenotypes of fibroblast exist in the lung. These phenotypic differences may partially explain the variable responses to injury and repair between proximal airways and distal lung/parenchyma in asthma and other respiratory diseases.

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Section: Discussionmentioning

confidence: 99%

Regional Fibroblast Heterogeneity in the Lung

Kotaru

Schoonover²,

Trudeau³

et al. 2006

Am J Respir Crit Care Med

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“…Airways-Although the presence of HA in the pulmonary secretions (26,27), (5,28), and cultured cells (15,29) of asthmatics has been demonstrated, to our knowledge the distribution of HA in asthmatic lung tissue has only been partially characterized (15). To address this we probed paraffin blocks of healthy control and asthmatic lung tissue with a biotinylated HABP using standard IHC methods ( Fig.…”

Section: Distribution Of Hyaluronan In Asthmatic and Control Lowermentioning

confidence: 99%

Hyaluronan and Its Heavy Chain Modification in Asthma Severity and Experimental Asthma Exacerbation

Lauer

Majors

Comhair

et al. 2015

Journal of Biological Chemistry

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Background: Hyaluronan has been linked to asthma severity and inflammation. Results: We characterized the hyaluronan levels and its heavy chain modification in an experimental model of human asthma exacerbation. Conclusion: These data implicate hyaluronan and its heavy chain modification in human asthma severity. Significance: Repetitive asthma exacerbations exacerbate hyaluronan pathobiology, which contribute to the chronic inflammation associated with this disease.

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“…For example, tenascin [56], lumican, biglycan and versican [57] are all present at elevated levels in the submucosa of asthmatic subjects. WESTERGREN-THORSSON [58] reported that subjects with the most hyperresponsive airways produced up to fourfold more total proteoglycan than subjects with less responsive airways. Laminin b 2 and a 1 staining [59] was also higher in biopsies from asthmatic subjects.…”

Section: Increased Deposition Of Extracellular Matrixmentioning

confidence: 99%

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

Boxall

Holgate²,

Davies³

2006

European Respiratory Journal

222

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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Correlation between airway responsiveness and proteoglycan production by bronchial fibroblasts from normal and asthmatic subjects

Cited by 87 publications

References 33 publications

Regional Fibroblast Heterogeneity in the Lung

Regional Fibroblast Heterogeneity in the Lung

Hyaluronan and Its Heavy Chain Modification in Asthma Severity and Experimental Asthma Exacerbation

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

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