MiR‐448‐5p inhibits TGF‐β1‐induced epithelial‐mesenchymal transition and pulmonary fibrosis by targeting Six1 in asthma

ZC Yang, ZH Qu, MJ Yi, YC Shan… - Journal of cellular …, 2019 - Wiley Online Library
ZC Yang, ZH Qu, MJ Yi, YC Shan, N Ran, L Xu, XJ Liu
Journal of cellular physiology, 2019Wiley Online Library
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 …
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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