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

Yu,Fei; Sun,Yan; Yu,Jiachen; Ding,Zhen; Wang,Jinrong; Zhang,Lanyun; Zhang,Tiejing; Bai,Yun; Wang,Yulin

doi:10.3892/mmr.2017.6413

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

Authors:
- Fei Yu
- Yan Sun
- Jiachen Yu
- Zhen Ding
- Jinrong Wang
- Lanyun Zhang
- Tiejing Zhang
- Yun Bai
- Yulin Wang
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Affiliations: Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Pediatrics, Traditional Chinese Hospital of Zibo, Zibo, Shandong 255300, P.R. China, Department of Pediatrics, Jilin Academy of Traditional Chinese Medicine, Changchun, Jilin 132000, P.R. China
Published online on: March 30, 2017 https://doi.org/10.3892/mmr.2017.6413
Pages: 2969-2976
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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