ORMDL3 knockdown in the lungs alleviates airway inflammation and airway remodeling in asthmatic mice via JNK1/2-MMP-9 pathway.
Biochem Biophys Res Commun
; 516(3): 739-746, 2019 08 27.
Article
em En
| MEDLINE
| ID: mdl-31255288
ABSTRACT
Orosomucoid-like protein 3 (ORMDL3) is a common mutation in many asthma patients and its effects on the specific pathogenesis of asthma are still unclear. Therefore, in this study, we used a mouse that specifically knockout the mouse ORDML3 gene to further study the mechanism. We used ovalbumin (OVA) to induce asthma in wild-type mice and ORMDL3 knockout mice. Lung ventilation resistance, airway inflammation, mucus hypersecretion, collagen deposition, the levels of inflammatory factors and the expression of ORDML3 and JNK1/2-MMP-9 pathway were detected. The results showed that ORMDL3 gene was highly expressed in clinical asthmatic children and mouse asthma model. Knocking down the ORMDL3 gene in the lung tissue of asthmatic mice can reduce airway hyperresponsiveness, airway inflammation, mucus secretion, and collagen deposition around the airway. After knocking down the lung tissue of mice, the IL-4, IL-5 and IL-13 concentrations in broncho alveolar lavage fluid of asthmatic mice were significantly decreased, and the activation of JNK1/2-MMP-9 pathway was inhibited in mouse lung tissue. Collectively, our results demonstrate that the ORMDL3 gene may aggravate asthma symptoms by activating the JNK1/2-MMP-9 pathway, which indicates that the ORMDL3 gene may be the key molecule for the next step of asthma targeted therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hipersensibilidade Respiratória
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Asma
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Metaloproteinase 9 da Matriz
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Proteína Quinase 8 Ativada por Mitógeno
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Proteína Quinase 9 Ativada por Mitógeno
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article