Follistatin-related protein 1 in asthma: miR-200b-3p interactions affect airway remodeling and inflammation phenotype

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  • 作者:Fen Liu, Jintao Zhang, Dong Zhang, Qian Qi, Wenjing Cui, Yun Pan, Xiaofei Liu, Jiawei Xu, Xinrui Qiao, Zihan Wang, Liang Dong
  • 期刊:INTERNATIONAL IMMUNOPHARMACOLOGY
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Follistatin-related protein 1 (FSTL1) is significantly associated with the asthma severity and outcome in humans and diverse mouse models of asthma. Previous studies have also suggested that FSTL1 could activate autophagy and NLRP3, thus playing as a causative agent in the asthma progression. However, mechanisms that regulate airway epithelial cell-specific FSTL1 expression and function in asthma are unknown. Here, we further evaluated the spatiotemporal relationships between the FSTL1 and asthma development through ovalbumin (OVA) -induced asthma models. Integrative analysis in asthmatics airway epithelium identifies microRNA (miR)-200b-3p as a novel upstream of FSTL1. Next, we collected airway biopsies, induced sputum, and blood samples isolated from asthmatics patients and the OVA-induced mouse model. We revealed that miR-200b-3p expression is downregulated in asthmatics airway epithelium, while its expression was negatively correlated with FSTL1. On this basis, the function and expression pattern analysis of miR-200b-3p were performed using miRNA-target prediction databases and long non-coding RNA (lncRNA) microarray assay. It is illustrated that miR-200b-3p, which is downregulated with pro-fibrotic stimulation of TGF-β1, could also be sponged by lncRNA PCAT19 and regulate FSTL1 expression in asthma progression. In vivo, miR-200b-3p overexpression in mice prevents OVA-induced airway remodeling and inflammation. Lastly, protective roles of miR-200b-3p are partly attributed to the direct and functional repression of FSTL1. Our findings suggest a crucial role for the miR-200b-3p/FSTL1 axis in regulating asthmatic's airway remodeling and inflammation phenotype.

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