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Published on: May 21, 2018
miR-27a is up regulated and promotes inflammatory response in sepsis
Zhongchuan Wang1, Zhengshang Ruan2, Yanfei Mao2
1Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Abstract:
MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of multiple target genes. Dysregulation of miRNAs is common in sepsis. Through microRNA microarray and qRT-PCR we found that the levels of miR-27a, miR-153 and miR-143 are up regulated, while let-7a, miR-218 and miR-129-5p are down regulated in lungs of septic mice. Knocking down of miR-27a down regulates expression levels of TNF-α and IL-6 significantly via reducing the phosphorylation level of NF-κB p65 and inhibiting its DNA binding activity. Furthermore, neutralisation of miR-27a up regulates PPARγ level, down regulates TNF-α expression, relieves pulmonary inflammation and promotes survival of septic mice, which demonstrates that miR-27a plays an important role in regulating inflammatory response in sepsis and provides a potential target for clinical sepsis research and treatment.
Insights
MicroRNAs (miRNAs) regulate gene expression and are dysregulated in sepsis. This study shows miR-27a inhibition reduces sepsis-induced inflammation and improves survival in mice, highlighting its therapeutic potential.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression.
- miRNA dysregulation is implicated in the pathogenesis of sepsis.
- Identifying specific miRNAs involved in sepsis is crucial for therapeutic development.
Purpose of the Study:
- To investigate the role of specific miRNAs in the pulmonary inflammatory response during sepsis.
- To identify potential miRNA targets for sepsis treatment.
Main Methods:
- MicroRNA microarray and quantitative real-time PCR (qRT-PCR) were used to profile miRNA expression in septic mouse lungs.
- Functional studies involved knocking down miR-27a and neutralizing its activity.
- Analysis included measuring levels of inflammatory cytokines (TNF-α, IL-6), NF-κB p65 phosphorylation, PPARγ expression, and assessing survival rates.
Main Results:
- Several miRNAs were found to be differentially expressed in septic mouse lungs, with miR-27a, miR-153, and miR-143 upregulated, and let-7a, miR-218, and miR-129-5p downregulated.
- Knockdown of miR-27a significantly reduced TNF-α and IL-6 levels by inhibiting NF-κB p65 phosphorylation and DNA binding.
- Neutralization of miR-27a increased PPARγ, decreased TNF-α, alleviated pulmonary inflammation, and improved survival in septic mice.
Conclusions:
- miR-27a plays a critical role in regulating the inflammatory response in sepsis.
- Targeting miR-27a presents a promising therapeutic strategy for sepsis treatment.
- Further research into miR-27a as a clinical target for sepsis is warranted.
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