ORMDL3 is associated with airway remodeling in asthma via the ERK/MMP-9 pathway.
ORMDL3 is associated with airway remodeling in asthma via the ERK/MMP-9 pathway.
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ORMDL3 通过 ERK/MMP-9 通路与哮喘气道重塑相关
DOI：
10.3892/mmr.2017.6413
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发表时间：
2017-05
影响因子：
3.4
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Yu F;Sun Y;Yu J;Ding Z;Wang J;Zhang L;Zhang T;Bai Y;Wang Y
ORMDL鞘脂生物合成调节因子3（ORMDL 3）与哮喘的发病机制有关，但其对气道重塑的影响尚不清楚。本研究检测了哮喘小鼠模型中ORMDL 3的表达水平。将小鼠分为哮喘模型组（n=10）、布地奈德组（n=10）和对照组（n=8）。在第1、7和14天用卵清蛋白（OVA）和氢氧化铝致敏诱导哮喘。随后，从第28天开始，每周三次将小鼠暴露于OVA。为了研究气道重塑的机制，在暴露于OVA之前，对6只动物给予100 µg/kg气雾剂布地奈德。通过组织学评估肺组织的状况，并使用免疫组织化学、逆转录定量聚合酶链反应和蛋白质印迹法定量ORMDL 3、磷酸化细胞外信号调节激酶（p-ERK）和基质金属肽酶-9（MMP-9）的表达水平。严重的炎症反应和气道重塑预处理布地奈德。ORMDL 3、磷酸化ERK和MMP-9的表达水平在哮喘模型组中显著增加;然而，在布地奈德预处理组中，它们的表达降低。ORMDL 3、p-ERK和MMP-9的表达水平与支气管壁厚度呈显著正相关。ORMDL 3表达与p-ERK、MMP-9呈显著正相关。因此，ORMDL 3表达增加可能通过p-ERK/MMP-9通路促进哮喘患者病理性气道重塑。
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.