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

Louise Margaret Harkness, Markus Weckmann, Matthias Kopp, Tim Becker, Anthony Wayne Ashton, Janette Kay Burgess*

*Korrespondierende/r Autor/-in für diese Arbeit
2 Zitate (Scopus)

Abstract

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.

OriginalspracheEnglisch
ZeitschriftJournal of Cellular and Molecular Medicine
Jahrgang21
Ausgabenummer12
Seiten (von - bis)3288-3297
Seitenumfang10
ISSN1582-1838
DOIs
PublikationsstatusVeröffentlicht - 01.12.2017

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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