title: ORMDL3 is associated with airway remodeling in asthma via the ERK/MMP-9 pathway.
abstract: 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), budesonide‑treated (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, phosphorylated‑extracellular‑signal regulated kinase (p‑ERK) and matrix metallopeptidase‑9 (MMP‑9) were quantified using immunohistochemistry, reverse transcription‑quantitative 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 MMP‑9 were significantly greater in the asthma‑model group; however, in the group pretreated with budesonide their expression was reduced. Expression levels of ORMDL3, p‑ERK and MMP‑9 were significantly positively correlated with bronchial wall thickness. ORMDL3 expression was significantly positively correlated with p‑ERK and MMP‑9. Therefore, increased ORMDL3 expression may induce the p‑ERK/MMP‑9 pathway to promote pathological airway remodeling in patients with asthma.
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Traditional Chinese Hospital of Zibo, Zibo, Shandong 255300, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Traditional Chinese Hospital of Zibo, Zibo, Shandong 255300, P.R. China.
authors.forename: Lanyun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Traditional Chinese Hospital of Zibo, Zibo, Shandong 255300, P.R. China.
authors.forename: Tiejing
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 132000, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000536:Aluminum Hydroxide / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; C583840:ORMDL3 protein, mouse; D019819:Budesonide; D000536:Aluminum Hydroxide; D010047:Ovalbumin; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9