lncRNA CRNDE Affects Th17/IL-17A and Inhibits Epithelial-Mesenchymal Transition in Lung Epithelial Cells Reducing Asthma Signs

Autor: Yu Yuan, Yi He, Binaya Wasti, Wentao Duan, Jingsi Jia, Zhifeng Chen, Xudong Xiang, Qingping Zeng
Rok vydání: 2023
Předmět:
Zdroj: Oxidative Medicine and Cellular Longevity. 2023:1-16
ISSN: 1942-0994
1942-0900
Popis: Background. Asthma treatment is difficult due to disease heterogeneity and comorbidities. In addition, the development of drugs targeting the underlying mechanisms of asthma remains slow. We planned to identify the most upregulated differentially expressed long noncoding RNA in asthma to explore its regulatory patterns and pathways in asthma. Methods. We sensitized mice using a mixture of ovalbumin, house dust mites, and lipopolysaccharide to establish an asthma mouse model. We also sensitized asthma cells with TGF-β1 in an in vitro model. We performed a microarray analysis to identify the lncRNA with the differential expression level in model mice. We applied hematoxylin and eosin and Masson’s trichrome stainings to mouse tissues to quantify the tissue damage extent. Next, we assess the levels of lncRNA CRNDE, miR-29a-3p, TGF-β1, MCL-1, E-cadherin, vimentin, and snail. We counted the percentages of Th17 cells using flow cytometry. Finally, we performed a dual-luciferase reporter assay to assess the association between lncRNA CRNDE and miR-29a-3p. Results. We successfully established asthma mouse/cell models and selected the lncRNA CRNDE for our study. Transfection of si-CRNDE reduced the degree of injury and inflammation in the mouse model and reversed the TGF-β1-induced epithelial-mesenchymal transition (EMT) in the cell model. Moreover, the E-cadherin level was upregulated, and the levels of IL-17A, vimentin, snail, and α-SMA were downregulated. We also discovered that lncRNA CRNDE negatively regulated miR-29a-3p and that this one in turn inhibited MCL-1 in mice. After lncRNA CRNDE expression downregulation, the level of miR-29a-3p was increased, and we detected reduced levels of MCL-1 and EMTs. Conclusions. lncRNA CRNDE expression downregulation led to reduced inflammation and reduced lung damage in mice with induced asthma, it inhibited the EMTs of lung epithelial cells via the miR-29a-3p/MCL-1 pathway, and it reduced the levels of Th17/IL-17A cells to reduce asthma signs.
Databáze: OpenAIRE
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