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

Abstract

Decorin (Dcn) is an extracellular matrix proteoglycan, which affects airway mechanics, airway-parenchymal interdependence, airway smooth muscle proliferation and apoptosis, and transforming growth factor-β 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 × 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, α-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-β and render it less bioavailable.

Detection and monitoring of localized matrix metalloproteinase upregulation in a murine model of asthma

“…We have previously seen significant, nonspecific uptake of ACPPs in proteoglycan-rich cartilage and areas of increased inflammation although this nonspecific uptake can be almost completely eliminated by attachment of ACPPs to high molecular weight carriers (36). Supporting this hypothesis, there have been reports that negatively charged proteoglycans are increased in murine models of OVA-induced asthma (32) and in patients with asthma (28,40).…”

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

“…Loss of caveolin-1 enhances ECM levels in chronic inflammation within the airway (7), whereas Rho kinase inhibition prevents ECM remodeling (235). Decorin, an ECM proteoglycan, can bind TGF-␤ and blunt ECM production within airways (191). Even infections can alter ECM production by ASM, exemplified by rhinovirus-induced increases in fibronectin and perlecan, particularly in asthmatic ASM (164).…”

Decorin as a multivalent therapeutic agent against cancer

“…Germane examples include immunomodulation [33,34], cutaneous wound healing [35], proper keratinocyte function [36], diabetic nephropathies [37], fetal membrane homeostasis [38], obesity and type II diabetes [39], allergen-induced asthma [40], allergic inflammation [41], delayed hypersensitivity reactions [42], hepatic fibrosis [43], myogenesis and muscular dystrophy [44,45], post myocardial infarction remodeling [46], and mediating proper vertebrate convergent extension [47]. Moreover, decorin has been identified as a potential biomarker for ischemic stroke [48], renal and pulmonary diseases [49-51] and for maintaining hematopoietic stem cell niches [52].…”