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Published on: March 1, 2019
Exploring the Regulatory Mechanism of CXCL16 Molecule-Related Antigen Presentation Using lncRNA-mRNA Co-Expression
Ting-Ting Liu1, Shuai Zheng1, Li-Xin Jia1
1Beijing Institute of Heart, Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling Cardiovascular Diseases, Ministry of Education, Collaborative Innovation Center for Cardiovascular Disorders, Beijing Anzhen Hospital, Capital Medical University, Beijing, People's Republic of China.
This study reveals key long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in Aspergillus fumigatus-induced asthma. These findings offer potential new targets for treating this allergic airway inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Bioinformatics
Background:
- Asthma is a chronic respiratory disease often exacerbated by fungal infections like Aspergillus fumigatus (A.f.).
- CXCL16 plays a role in immune responses, but its precise regulatory mechanism in A.f.-induced asthma, particularly involving non-coding RNAs, remains unclear.
Purpose of the Study:
- To investigate the regulatory mechanisms of CXCL16 in A.f.-induced asthma by analyzing long non-coding RNA (lncRNA) and mRNA expression profiles.
- To identify potential therapeutic targets for A.f.-induced asthma by constructing and analyzing a lncRNA-mRNA co-expression network.
Main Methods:
- Utilized a mouse model of A.f.-induced asthma, comparing wild-type and CXCL16 knockout mice.
- Employed high-throughput sequencing to profile lncRNA and mRNA expression in lung tissues.
- Constructed a lncRNA-mRNA co-expression network and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
- Validated key findings using RT-PCR and ELISA in a CXCL16 neutralizing antibody model.
Main Results:
- CXCL16 knockout mice exhibited significant alterations in lncRNA and mRNA expression compared to wild-type mice.
- A co-expression network identified 244 differentially expressed lncRNAs and 49 differentially expressed mRNAs.
- Hub genes and four specific lncRNAs (NONMMUT026034, NONMMUT028184, NONMMUT016537, and NONMMUT043155) were validated as key players.
Conclusions:
- The study elucidates the complex lncRNA-mRNA regulatory network in A.f.-induced asthma.
- Identified four key lncRNAs as potential therapeutic targets for modulating CXCL16-mediated antigen presentation in asthma.
- Provides novel insights into the molecular mechanisms underlying A.f.-induced allergic airway inflammation.
