MiR-448-5p inhibits TGF-β1-induced epithelial-mesenchymal transition and pulmonary fibrosis by targeting Six1 in asthma |
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Authors: | Zhao-Chuan Yang Zheng-Hai Qu Ming-Ji Yi Yan-Chun Shan Ni Ran Lei Xu Xin-Jie Liu |
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Institution: | 1. Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China;2. Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, China;3. Department of Child Health Care, The Affiliated Hospital of Qingdao University, Qingdao, China |
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Abstract: | MicroRNAs (miRNAs) are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation. The aim of this study was to explore how miR-448-5p affects airway remodeling and transforming growth factor-β1 (TGF-β1)-stimulated epithelial-mesenchymal transition (EMT) by targeting Sine oculis homeobox homolog 1 (Six1) in asthma. Asthmatic mice models with airway remodeling were induced with ovalbumin solution. MiRNA expression was evaluated using quantitative real-time polymerase chain reaction. Transfection studies of bronchial epithelial cells were performed to determine the target genes. A luciferase reporter assay system was applied to identify whether Six1 is a target gene of miR-448-5p. In the current study, we found that miR-448-5p was dramatically decreased in lung tissues of asthmatic mice and TGF-β1-stimulated bronchial epithelial cells. In addition, the decreased level of miR-448-5p was closely associated with the increased expression of Six1. Overexpression of miR-448-5p decreased Six1 expression and, in turn, suppressed TGF-β1-mediated EMT and fibrosis. Next, we predicted that Six1 was a potential target gene of miR-448-5p and demonstrated that miR-448-5p could directly target Six1. An SiRNA targeting Six1 was sufficient to suppress TGF-β1-induced EMT and fibrosis in 16HBE cells. Furthermore, the overexpression of Six1 partially reversed the protective effect of miR-448-5p on TGF-β1-mediated EMT and fibrosis in bronchial epithelial cells. Taken together, the miR-448-5p/TGF-β1/Six1 link may play roles in the progression of EMT and pulmonary fibrosis in asthma. |
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Keywords: | airway remodeling asthma epithelial-mesenchymal transition (EMT) microRNA-448-5p Sine oculis homeobox homolog 1 (Six1) |
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