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Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Differential expression profile of plasma exosomal microRNAs in acute type A aortic dissection with acute lung injury
Chiyuan Zhang1,2, Hui Bai1, Lei Zhang1
1Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Xiangya Rd 87, Changsha, 410008, Hunan, China.
Abstract:
MicroRNAs (miRNAs) packaged into exosomes mediate cell communication and contribute to the pathogenesis of acute type A aortic dissection (ATAAD) with acute lung injury (ALI). The expression profile of plasma exosomal miRNAs in ATAAD patients with ALI hasn't been identified. We performed a miRNA-sequencing to analyze the differentially expressed miRNAs (DE-miRNAs) of circulating exosomes in ATAAD patients with ALI compared to patients without ALI, founding 283 specific miRNAs in two groups. We respectively selected the top 10 downregulated and upregulated DE-miRNAs for further studies. The predicted transcription factors (TFs) of these DE-miRNAs were SMAD2, SRSF1, USF1, etc. The Gene Ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) analysis predicted their target genes mainly involved acute inflammatory response, cell junction, cytoskeleton, NF-κB signaling pathway, etc. Construction and analysis of the PPI network revealed that RHOA and INSR were considered hub genes with the highest connectivity degrees. Moreover, we confirmed two exosomal miRNAs (hsa-miR-485-5p and hsa-miR-206) by real-time quantitative polymerase chain reaction (RT-qPCR) in a validation cohort. Our study identified a plasma exosomal miRNAs signature related to ATAAD with ALI. Certain DE-miRNAs may contribute to the progression of this disease, which help us better understand the pathogenesis of ATAAD with ALI.
Insights
This study identifies specific exosomal microRNAs (miRNAs) in the blood of patients with acute type A aortic dissection and acute lung injury. These circulating miRNAs may play a role in disease development.
Area of Science:
- Biochemistry
- Molecular Biology
- Genomics
Background:
- Exosomes facilitate intercellular communication via microRNAs (miRNAs), contributing to diseases like acute type A aortic dissection (ATAAD) with acute lung injury (ALI).
- The specific profile of plasma exosomal miRNAs in ATAAD patients with ALI remains largely uncharacterized.
Purpose of the Study:
- To identify differentially expressed miRNAs (DE-miRNAs) in circulating exosomes from ATAAD patients with ALI compared to those without ALI.
- To elucidate the potential roles of these DE-miRNAs in the pathogenesis of ATAAD with ALI.
Main Methods:
- MiRNA sequencing was employed to analyze plasma exosomal miRNAs.
- Bioinformatic analyses including transcription factor prediction, Gene Ontology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network construction were performed.
- Real-time quantitative polymerase chain reaction (RT-qPCR) was used for validation.
Main Results:
- A total of 283 DE-miRNAs were identified between the two groups.
- Top downregulated and upregulated DE-miRNAs were selected, with predicted transcription factors including SMAD2, SRSF1, and USF1.
- Target gene analysis indicated involvement in acute inflammatory response, cell junction, cytoskeleton, and the NF-κB signaling pathway. RHOA and INSR emerged as key hub genes.
- Two exosomal miRNAs, hsa-miR-485-5p and hsa-miR-206, were validated.
Conclusions:
- A distinct plasma exosomal miRNA signature associated with ATAAD and ALI was identified.
- These DE-miRNAs may contribute to the progression of ATAAD with ALI, offering insights into disease pathogenesis.
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