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lncRNA CRNDE Affects Th17/IL-17A and Inhibits Epithelial-Mesenchymal Transition in Lung Epithelial Cells Reducing
Yu Yuan1, Yi He1, Binaya Wasti1
1Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
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.
Insights
This study identified long noncoding RNA CRNDE as a key player in asthma. Downregulating CRNDE reduced inflammation and lung damage by inhibiting epithelial-mesenchymal transition via the miR-29a-3p/MCL-1 pathway.
Area of Science:
- Molecular Biology
- Immunology
- Respiratory Medicine
Background:
- Asthma treatment is challenging due to disease complexity and comorbidities.
- Developing targeted therapies for asthma's underlying mechanisms is slow.
- Identifying key regulatory molecules like long noncoding RNAs (lncRNAs) is crucial for understanding asthma pathogenesis.
Purpose of the Study:
- To identify upregulated differentially expressed lncRNAs in asthma.
- To explore the regulatory patterns and pathways of identified lncRNAs in asthma.
- To investigate the role of lncRNA CRNDE in asthma development and progression.
Main Methods:
- Established mouse and in vitro asthma models.
- Utilized microarray analysis to identify differentially expressed lncRNAs.
- Assessed lncRNA CRNDE, miR-29a-3p, and related protein levels, alongside inflammation markers and epithelial-mesenchymal transition (EMT) indicators.
- Performed dual-luciferase reporter assays to confirm interactions.
Main Results:
- Successfully established asthma models and identified lncRNA CRNDE.
- Downregulation of lncRNA CRNDE reduced lung injury and inflammation in mice.
- lncRNA CRNDE negatively regulated miR-29a-3p, which in turn inhibited MCL-1, thereby impacting EMT.
- Observed increased E-cadherin and decreased vimentin, snail, and α-SMA levels upon CRNDE downregulation.
Conclusions:
- Downregulating lncRNA CRNDE alleviates asthma-related inflammation and lung damage.
- lncRNA CRNDE inhibition suppresses epithelial-mesenchymal transition through the miR-29a-3p/MCL-1 pathway.
- Reduced Th17/IL-17A cell levels contribute to the therapeutic effect of CRNDE downregulation in asthma.
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