Effects of microRNA-19b on airway remodeling, airway inflammation and degree of oxidative stress by targeting TSLP through the Stat3 signaling pathway in a mouse model of asthma
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Ling Ye1,*, Yan Mou1,*, Jian Wang1 and Mei-Ling Jin1
1Department of Respiratory Medicine, Affiliated Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China
*These authors have contributed equally to this work
Mei-Ling Jin, email: email@example.com
Keywords: microRNA-19b, asthma, thymic stromal lymphopoietin, Stat3, ovalbumin
Received: June 20, 2016 Accepted: February 12, 2017 Published: April 20, 2017
This study explored the effects of microRNA-19b (miR-19b) on airway remodeling, airway inflammation, and degree of oxidative stress in a mouse model of asthma. Bioinformatics analyses and dual luciferase reporter gene assays revealed that thymic stromal lymphopoietin (TSLP) is a direct target of miR-19b. An asthma model was established via ovalbumin (OVA) sensitization and challenge in 72 female BALB/c mice. Mice were then assigned to saline, OVA-sensitized, saline+miR-19b mimics, saline+anti-TSLP, OVA-sensitized+miR-19b mimics, OVA-sensitized+mimics scramble, OVA-sensitized+anti-TSLP, and OVA-sensitized+IgG2a groups. Pathological morphology changes were detected through hematoxylin/eosin, Masson, and periodic acid-Schiff staining. miR-19b was downregulated while TSLP and Stat3 were upregulated in the OVA-sensitized group compared with the saline group. Bronchoalveolar lavage fluid samples from OVA-sensitized mice showed increased total protein, IL-4, IL-5 and IL-6 levels, numbers of inflammatory cells, eosinophils, neutrophils, mononuclear macrophages and lymphocytes, and eosinophil% compared to controls. Lung tissues from sensitized mice exhibited decreased superoxide dismutase activity and increased methane dicarboxylic aldehyde levels. The effects of OVA sensitization were reversed in the OVA-sensitized+miR-19b mimics and OVA-sensitized+anti-TSLP groups. These findings suggest miR-19b reduces airway remodeling, airway inflammation, and degree of oxidative stress by inhibiting Stat3 signaling through TSLP downregulation in a mouse asthma model.
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