Journal of Asthma and Allergy (May 2021)
MiR-21-5p in Macrophage-Derived Exosomes Targets Smad7 to Promote Epithelial Mesenchymal Transition of Airway Epithelial Cells
Abstract
Xiang Li, Nan Yang, Qi Cheng, Han Zhang, Fen Liu, Yunxiao Shang Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of ChinaCorrespondence: Yunxiao ShangDepartment of Pediatrics Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, People’s Republic of ChinaEmail [email protected]: Asthma is usually associated with airway inflammation and airway remodeling. Epithelial mesenchymal transition (EMT) often occurs in airway remodeling. The purpose of this study is to identify the effect of miR-21-5p and Smad7 signaling pathway in macrophage-derived exosomes on EMT of airway epithelial cells.Methods: HE staining and Masson staining were used to verify the successful establishment of the asthma model. The levels of epithelial cell adhesion factor and stromal cell markers were detected by Western blot. The levels of miR-21-5p were detected by qRT-PCR. The expression of miR-21-5p in lung tissue was further verified by fluorescence in situ hybridization (FISH). Exosome morphology was observed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Luciferase reporter assay was applied to analyze the interaction of miR-21-5p with Smad7.Results: The expression of miR-21-5p was upregulated in macrophages of rats in vivo with OVA-induced asthma. In vitro cultured alveolar macrophages stimulated by LPS could secrete exosomes with high levels of miR-21-5p. The exosome-derived miR-21-5p promotes EMT in rat tracheal epithelial cells through TGFβ 1/Smad signaling pathway by downregulating Smad7. This process can be blocked by miR-21-5p inhibitor.Conclusion: Rat alveolar macrophages produced high levels of miR-21-5p-containing exosomes, which transported miR-21-5p to tracheal epithelial cells, thus promoting EMT through TGF-β 1/Smad signaling pathway by targeting Smad7.Keywords: asthma, exosomes, miRNA, miR-21-5p, Smad7, epithelial mesenchymal transition
