A role for decorin in a murine model of allergen-induced asthma

作者：Marchica Cinzia L; Pinelli Valentina; Borges Marcos; Zummer Jaryd; Narayanan Venkatesan; Iozzo Renato V; Ludwig Mara S^*

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2011, 300(6): L863-L873.

DOI：10.1152/ajplung.00300.2009

• animal model
• transforming growth factor-beta
• proteoglycans
• airway remodeling

Marchica CL, Pinelli V, Borges M, Zummer J, Narayanan V, Iozzo RV, Ludwig MS. A role for decorin in a murine model of allergen-induced asthma. Am J Physiol Lung Cell Mol Physiol 300: L863-L873, 2011. First published March 4, 2011; doi:10.1152/ajplung.00300.2009.-Decorin (Dcn) is an extracellular matrix proteoglycan, which affects airway mechanics, airway-parenchymal interdependence, airway smooth muscle proliferation and apoptosis, and transforming growth factor-beta bioavailability. As Dcn deposition is differentially altered in asthma, we questioned whether Dcn deficiency would impact the development of allergen-induced asthma in a mouse model. Dcn(-/-) and Dcn(+/+) mice (C57Bl/6) were sensitized with ovalbumin (OA) and challenged intranasally 3 days/wk X 3 wk. After OA challenge, mice were anesthetized, and respiratory mechanics measured under baseline conditions and after delivery of increasing concentrations of methacholine aerosol. Complex impedance was partitioned into airway resistance and tissue elastance and damping. Bronchoalveolar lavage was performed. Lungs were excised, and tissue sections evaluated for inflammatory cell influx, alpha-smooth muscle actin, collagen, biglycan, and Dcn deposition. Changes in TH-2 cytokine mRNA and protein were also measured. Airway resistance was increased in OA-challenged Dcn(+/+) mice only (P < 0.05), whereas tissue elastance and damping were increased in both OA-challenged Dcn(+/+) and Dcn(+/+), but more so in Dcn(+/+) mice (P < 0.001). Inflammation and collagen staining within the airway wall were increased with OA in Dcn(+/+) only (P < 0.001 and P < 0.01, respectively, vs. saline). IL-5 and IL-13 mRNA were increased in lung tissue of OA-challenged Dcn(+/+) mice. Dcn deficiency resulted in more modest OA-induced hyperresponsiveness, evident at the level of the central airways and distal lung. Differences in physiology were accompanied by differences in inflammation and remodeling. These findings may be, in part, due to the well-described ability of Dcn to bind transforming growth factor-beta and render it less bioavailable.

• 出版日期2011-6