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Tumstatin regulates the angiogenic and inflammatory potential of airway smooth muscle extracellular matrix.
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.
Authors : Harkness Louise Margaret , Weckmann Markus , Kopp Matthias , Becker Tim , Ashton Anthony Wayne , Burgess Janette Kay ,
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Pathways :
WP1991: SRF and miRs in Smooth Muscle Differentiation and Proliferation
WP2081: SRF and miRs in Smooth Muscle Differentiation and Proliferation
WP1040: Inflammatory Response Pathway
WP1060: Matrix Metalloproteinases
WP1088: Striated Muscle Contraction
WP1113: Cytokines and Inflammatory Response
WP1156: Inflammatory Response Pathway
WP1176: Matrix Metalloproteinases
WP129: Matrix Metalloproteinases
WP1316: Striated Muscle Contraction
WP1403: AMPK signaling
WP1438: Influenza A virus infection
WP1864: Muscle contraction
WP1946: Cori Cycle
WP1963: The effect of Glucocorticoids on target gene expression
WP2005: Muscle cell TarBase
WP2012: miRs in Muscle Cell Differentiation
WP2076: miRs in Muscle Cell Differentiation
WP2118: Arrhythmogenic right ventricular cardiomyopathy
WP216: Striated Muscle Contraction
WP222: Cytokines and Inflammatory Response (BioCarta)
WP271: Cytokines and Inflammatory Response (BioCarta)
WP278: Matrix Metalloproteinases
WP316: Striated Muscle Contraction
WP383: Striated Muscle Contraction
Related Genes :
[COL4A3] Collagen alpha-3(IV) chain (Goodpasture antigen) [Cleaved into: Tumstatin]
[Col4a3] Collagen alpha-3(IV) chain [Cleaved into: Tumstatin]
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