Interference of miR-943-3p with secreted frizzled-related proteins4 (SFRP4) in an asthma mouse model
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The aim of this study is to investigate the potential roles of miR-943-3p and its target gene secreted frizzled-related proteins4 (SFRP4) in allergic asthma and elucidate its underlying mechanism, which may prompt a new clue about developing novel treatments of this disease. An allergic asthma mouse model was generated by challenging with ovalbumin (OVA); lung pathological features of mice were viewed using H&E staining; thickness of subepithelial fibrosis and smooth muscle was measured using Masson’s trichrome staining. Inflammatory cells from bronchoalveolar lavage fluid (BALF) were counted based on Diff-Quik staining and morphometric analysis. Expressions of miR-943-3p, SFRP4 and Wnt signal pathway-associated proteins were detected using RT-PCR or immunoblotting, respectively. SFRP4 was downregulated in the bronchial biopsies of allergic asthma patients and represented a unique intersection between differentially expressed genes (DEGs) and genes in the Wnt signal pathway. Both miR-943-3p upregulation and SFRP4 downregulation were detected in allergic asthma patients and OVA-induced mice. Besides, OVA-induced mice possessed more inflammatory cells in BALF including macrophage (mac), eosinophil (eos), lymphocyte (lym) and neutrophil (neu), higher expression of collagen, β-catenin and c-Myc as well as thicker subepithelial fibrosis and smooth muscle in lung than control mice. In vivo delivery of miR-943-3p agomir worsened these symptoms, while both miR-943-3p antagomir and Ad-SFRP4 administration effectively alleviated this disease. Taken together, miR-943-3p accelerated the progression of airway inflammation and remodeling in allergic asthma via suppressing the activity of SFRP4 through Wnt signaling pathway in asthma patients and OVA-induced mice.
KeywordsAllergic asthma SFRP4 miR-943-3p Wnt signaling pathway Secreted protein
This study was supported by the Science and Technology Commission of Shanghai Municipality Traditional Chinese Medicine (TCM specialist) Specialized Personnel Plan (ZY3-RCPY-3-1027), Shanghai Special Program for Children’s Health Service Capacity Building High Pediatric Overseas Training Team Cultivation-Pediatrics of Integrated Traditional Chinese and Western Medicine (GDEK201704) and Important Subject Construction of Shanghai Health and Family Planning System-Pediatrics of Integrative Chinese and Western Medicine (2016ZB0104-02).
Compliance with ethical standards
Ethics approval and consent to participate
This study was authorized by the Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, who obtained written informed consents from all the participants.
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare that they have no conflicts of interest.
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