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Interference of miR-943-3p with secreted frizzled-related proteins4 (SFRP4) in an asthma mouse model

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Abstract

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.

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Funding

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).

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Authors and Affiliations

  1. Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, No. 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, China

    Jian Shen, Jun Zhao & Qing-yan Ye

  2. Department of Clinical Laboratory, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, China

    Xi-dong Gu

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  1. Jian Shen
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Correspondence to Jian Shen.

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This study was authorized by the Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, who obtained written informed consents from all the participants.

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Shen, J., Zhao, J., Ye, Qy. et al. Interference of miR-943-3p with secreted frizzled-related proteins4 (SFRP4) in an asthma mouse model. Cell Tissue Res 378, 67–80 (2019). https://doi.org/10.1007/s00441-019-03026-6

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