| First Author | Walker JKL | Year | 2017 |
| Journal | Am J Respir Cell Mol Biol | Volume | 57 |
| Issue | 6 | Pages | 702-710 |
| PubMed ID | 28787175 | Mgi Jnum | J:267336 |
| Mgi Id | MGI:6258976 | Doi | 10.1165/rcmb.2017-0095OC |
| Citation | Walker JKL, et al. (2017) Targeted HAS2 Expression Lessens Airway Responsiveness in Chronic Murine Allergic Airway Disease. Am J Respir Cell Mol Biol 57(6):702-710 |
| abstractText | Hyaluronan (HA), a major component of the extracellular matrix, is secreted by airway structural cells. Airway fibroblasts in allergic asthma secrete elevated levels of HA in association with increased HA 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. To examine this hypothesis, transgenic mice in which the alpha-smooth muscle actin (alpha-SMA) promoter drives HAS2 expression were generated. Mixed male and female alpha-SMA-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 HA-binding protein (HABP) and alpha-SMA, as well as Masson's trichrome stain. Staining of lung tissue demonstrated significantly increased peribronchial HA, alpha-SMA, and collagen deposition in OVA-challenged alpha-SMA-HAS2(+) mice compared with alpha-SMA-HAS2(-) mice. Unexpectedly, OVA-challenged alpha-SMA-HAS2(+) mice displayed significantly reduced airway responsiveness to methacholine compared with similarly treated alpha-SMA-HAS2(-) mice. The total numbers of inflammatory cell types in the bronchoalveolar lavage fluid did not differ significantly between OVA-challenged alpha-SMA-HAS2(+) mice and alpha-SMA-HAS2(-) mice. We conclude that allergen-challenged mice that overexpress HAS2 in myofibroblasts and smooth muscle cells develop increased airway fibrosis, which lessens airway hyperresponsiveness to bronchoconstrictors. |
