Reduction of Tumstatin in Asthmatic Airways Contributes to Angiogenesis, Inflammation, and Hyperresponsiveness

Burgess, Janette K.; Boustany, Sarah; Moir, Lyn M.; Weckmann, Markus; Lau, Justine Y; Grafton, Karryn; Baraket, Melissa; Hansbro, Philip M.; Hansbro, Nicole G.; Foster, Paul S.; Black, Judith L.; Oliver, Brian G.

doi:10.1164/rccm.200904-0631oc

Cited by 66 publications

(118 citation statements)

References 59 publications

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“…This reflects the distribution of tumstatin protein, we have previously reported in human lung tissue 19. Given the absence of tumstatin production by ASM cells, this study investigated the exogenous effects of this matrikine that is potentially released from the non‐asthmatic ECM to regulate tissue homeostasis.…”

Section: Discussionmentioning

confidence: 90%

“…When introduced to animal models of asthma tumstatin resolves features of airway remodelling and inflammation and improves lung function 19, 24. The current study characterized the role of tumstatin in the maintenance of airway tissue homeostasis, through regulation of the ASM‐derived ECM, and the potential contribution of the absence of tumstatin in asthmatic airways to the pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Tumstatin regulates the angiogenic and inflammatory potential of airway smooth muscle extracellular matrix

Harkness

Weckmann

Kopp

et al. 2017

J Cellular Molecular Medi

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The extracellular matrix (ECM) creates the microenvironment of the tissue; an altered ECM in the asthmatic airway may be central in airway inflammation and remodelling. Tumstatin is a collagen IV‐derived matrikine reduced in the asthmatic airway wall that reverses airway inflammation and remodelling in small and large animal models of asthma. This study hypothesized that the mechanisms underlying the broad asthma‐resolving effects of tumstatin were due to autocrine remodelling of the ECM. Neutrophils and endothelial cells were seeded on decellularized ECM of non‐asthmatic (NA) or asthmatic (A) airway smooth muscle (ASM) cells previously exposed to tumstatin in the presence or absence of a broad matrix metalloproteinase inhibitor, Marimastat. Gene expression in NA and A ASM induced by tumstatin was assessed using RT‐PCR arrays. The presence of tumstatin during ECM deposition affected neutrophil and endothelial cell properties on both NA and A ASM‐derived matrices and this was only partly due to MMP activity. Gene expression patterns in response to tumstatin in NA and A ASM cells were different. Tumstatin may foster an anti‐inflammatory and anti‐angiogenic microenvironment by modifying ASM‐derived ECM. Further work is required to examine whether restoring tumstatin levels in the asthmatic airway represents a potential novel therapeutic approach.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Tumstatin regulates the angiogenic and inflammatory potential of airway smooth muscle extracellular matrix

Harkness

Weckmann

Kopp

et al. 2017

J Cellular Molecular Medi

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“…However, in chronic inflammatory conditions such as asthma, the balance between angiogenic and angiostatic mediators is altered leading to unregulated vessel formation [45,46] and it is now widely accepted that chronic inflammation is associated with angiogenesis.…”

Section: Angiogenic Processesmentioning

confidence: 99%

“…In addition to VEGF, angiogenin levels are also increased in BALf and in bronchial biopsies from asthmatic subjects [46,50] and are found to induce vascular endothelial cell proliferation, migration and tubule formation in vitro [26]. TGFβ1 and bradykinin also induce VEGF secretion in cultured human ASM cells, fibroblasts and bronchial epithelial cells [26,45,52].…”

Section: The Role Of Vegf In Vascular Remodelling and Airway Inflammamentioning

confidence: 99%

Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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In chronic lung disorders such as in asthma and chronic obstructive pulmonary disease (COPD) there is increased bronchial angiogenesis and remodelling of pulmonary vessels culminating to altered bronchial and pulmonary circulation. The involvement of residential cells such as endothelial cells, smooth muscle cells and pulmonary fibroblasts, all appear to have a crucial role in the progression of vascular inflammation and remodelling. The regulatory abnormalities, growth factors and mediators implicated in the pulmonary vascular changes of asthma and COPD subjects and potential therapeutic targets have been described in this review.

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“…Analyzing BALf is one of the prime parameters to understand the underlying disease pathology in prominent mice models of major respiratory diseases, including asthma [27][28][29], COPD [30,31], and pulmonary fibrosis [32]. Moreover, the application of BALF is not only restricted to quantifying the inflammatory cells, it is also employed to determine the viral titre in various viral infections [3,30].…”

Section: Clinical Utility Of Balf Collectionmentioning

confidence: 99%

Aspiration techniques for bronchoalveolar lavage in translational respiratory research: Paving the way to develop novel therapeutic moieties

Dua

Shukla

Hansbro³

2017

J Biol Methods

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Bronchoalveolar lavage (BAL) is a simple, yet informative tool in understanding the immunopathology of various lung diseases via quantifying various inflammatory cells, cytokines and growth factors. At present, this traditional method is often blended with several robust and sophisticated molecular and biological techniques sustaining the significance and longevity of this technique. Crucially, the existence of slightly distinct approaches and variables employed at different laboratories around the globe in performing BAL aspiration indeed demands an utmost need to optimize and develop an effective, cost-effective and a reproducible technique. This mini review will be of importance to the biological translational scientist, particularly respiratory researchers in understanding the fundamentals and approaches to apply and consider with BAL aspiration techniques. This will ensure generating a meaningful and clinically relevant data which in turn accelerate the development of new and effective therapeutic moieties for major respiratory conditions.

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Reduction of Tumstatin in Asthmatic Airways Contributes to Angiogenesis, Inflammation, and Hyperresponsiveness

Cited by 66 publications

References 59 publications

Tumstatin regulates the angiogenic and inflammatory potential of airway smooth muscle extracellular matrix

Tumstatin regulates the angiogenic and inflammatory potential of airway smooth muscle extracellular matrix

Pulmonary vascular changes in asthma and COPD

Aspiration techniques for bronchoalveolar lavage in translational respiratory research: Paving the way to develop novel therapeutic moieties

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