ORMDL3 is associated with airway remodeling in asthma via the ERK/MMP-9 pathway.

ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) has been previously implicated in asthma pathogenesis, its effect on airway remodeling remains to be elucidated. The present study examined the expression levels of ORMDL3 in a mouse model of asthma. Mice were divided into three groups: Asthmatic model (n=10), budesonide­treated (n=10) and a control group (n=8). Asthma was induced by sensitization with ovalbumin (OVA) and aluminum hydroxide on day 1, 7 and 14. Subsequently mice were exposed to OVA three times per week from day 28. In order to investigate the mechanism of airway remodeling 100 µg/kg aerosol budesonide was administered to 6 animals prior to exposure to OVA. The condition of lung tissues was assessed through histology, and the expression levels of ORMDL3, phosphorylated­extracellular­signal regulated kinase (p­ERK) and matrix metallopeptidase­9 (MMP­9) were quantified using immunohistochemistry, reverse transcription­quantitative polymerase chain reaction and western blotting. A severe inflammatory response and airway remodeling were pretreatment with budesonide. Expression levels of ORMDL3, phosphorylated (p)­ERK and MMP­9 were significantly greater in the asthma­model group; however, in the group pretreated with budesonide their expression was reduced. Expression levels of ORMDL3, p­ERK and MMP­9 were significantly positively correlated with bronchial wall thickness. ORMDL3 expression was significantly positively correlated with p­ERK and MMP­9. Therefore, increased ORMDL3 expression may induce the p­ERK/MMP­9 pathway to promote pathological airway remodeling in patients with asthma.