Julia Walker published an article entitled "Targeted HAS2 Expression Lessens Airway Responsiveness in Chronic Murine Allergic Airway Disease" in the August issue of the American Journal of Respiratory Cell and Molecular Biology. Co-authors include experts from Duke University Medicine, National Institute of Environmental Health Sciences, Cedars-Sinai Medical Center, and the University of Arizona College of Medicine.

Abstract: Hyaluronan (HA), a major component of extracellular matrix, is secreted by airway structural cells. For example, airway fibroblasts in allergic asthma secrete elevated levels of HA in association with increased hyaluronan synthase 2 (HAS2) expression. Thus, we hypothesized that HA accumulation in the airway wall may contribute to airway remodeling and hyperresponsiveness in allergic airways disease. METHODS: Transgenic mice were generated in which the smooth muscle α-actin (αSMA) promoter drives HAS2 expression. Mixed male and female αSMA-HAS2 mice (HAS2+ mice, n=16; HAS2- mice, n=13) were sensitized via intraperitoneal injection, and then chronically challenged with aerosolized ovalbumin (OVA) for 6 weeks. To test airway responsiveness, increasing doses of methacholine were delivered intravenously, and airway resistance was measured using the forced oscillation technique. HA, cytokines, and cell types were analyzed in bronchoalveolar lavage fluid, serum and whole lung homogenates. Lung sections were stained using antibodies specific for hyaluronan binding protein (HABP) and αSMA, as well as Masson's trichrome stain. RESULTS: Staining of lung tissue demonstrated significantly increased peribronchial HA, αSMA, and collagen deposition in OVA-challenged αSMA-HAS2+ mice compared to αSMA-HAS2- mice. Unexpectedly, OVA-challenged αSMA-HAS2+ displayed significantly reduced airway responsiveness to methacholine compared to similarly-treated αSMA-HAS2- mice. Total numbers of inflammatory cell types in the bronchoalveolar lavage fluid of OVA-challenged αSMA-HAS2+ mice were not significantly different from that of OVA-challenged αSMA-HAS2- mice. CONCLUSIONS: Allergen-challenged mice that overexpress HAS2 in myofibroblasts and smooth muscle cells develop increased airway fibrosis, which lessens airway hyperresponsiveness to bronchoconstrictors.