Tumstatin deficiency implicated in asthma-associated airway remodeling
MedWire News: A deficiency of tumstatin in lung tissue may contribute to airway remodeling in patients with asthma, results of an Australian study suggest.
“Asthma is an inflammatory disease characterized by airway remodeling. A prominent feature of this remodeling is angiogenesis, which is an increase in the number and size of the blood vessels,” explain Janette Burgess (University of Sydney, New South Wales), and team.
They add that although endogenous angiogenic inhibitors, including tumstatin (the NC1 domain of the α-3 chain of collagen IV), are present in fluids and tissues in the body, levels of tumstatin in lung tissue from asthma patients have not been assessed.
To address this, and to examine the potential for tumstatin to regulate angiogenesis and inflammation, the team studied bronchial biopsies, bronchoalveolar lavage fluid, and serum samples collected from 25 patients with asthma and 44 individuals without the condition.
Analysis revealed that tumstatin levels were 18.5-fold lower in lung tissue samples from patients with asthma compared with those from nonasthmatic individuals. Indeed, levels of tumstatin were barely detectable in samples from the patients with asthma.
The researchers also found that, in vitro, tumstatin inhibited pulmonary endothelial cell tube formation in a dose-related manner, indicating a potential role in attenuating angiogenesis.
To obtain further insights into the role of tumstatin in the regulation of angiogenesis during allergic airway inflammation, the researchers studied a mouse model of chronic ovalbumin-induced allergic airways disease.
They found that tumstatin suppressed angiogenesis, airway hyper-responsiveness, inflammatory cell infiltration, and mucus secretion, and decreased levels of vascular endothelial growth factor and interleukin-13.
Burgess and team conclude: “The observation that tumstatin is decreased in asthmatic airways and inhibits airway hyper-responsiveness and angiogenesis demonstrates the potential use of antiangiogenic agents such as tumstatin as a therapeutic intervention in diseases that are characterized by aberrant angiogenesis and tissue remodeling, such as asthma.”
The research is published in the American Journal of Respiratory and Critical Care Medicine.
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By Mark Cowen