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Updated: Mar 27, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Alleviation of Lipopolysaccharides-Induced Acute Lung Injury by MiR-454
Zhengang Tao1, Ying Yuan, Qingwu Liao
1Emergency Department, Zhongshan Hospital, Shanghai, China.
Background/Aims:
Although acute lung injury (ALI) is an important and common disease in humans, its pathogenesis is poorly understood and its therapeutic outcome has not been significantly improved in the past years. Here, we examined whether application of microRNAs might inhibit the ALI-associated lung inflammatory, and subsequently reduce the injury.
Methods:
In vitro, we performed bioinformatics analyses to identify the miRNAs that target the most important chemo-attractive factor CXCL12, and confirmed that the binding was functional by luciferase reporter assay. We prepared adeno-associated virus (AAV) carrying miRNA mimics or null control. We expressed miRNA in mouse lung through i.v. injection of AAV and then we used Lipopolysaccharides (LPS) to induce ALI in mice. We analyzed the changes in permeability index and production of inflammatory cytokines in mouse lung, and we also verified the effects of virus-mediated gene expression by examining the levels of miRNAs and CXCL12 in lung by RT-qPCR and ELISA, and by quantifying the recruited inflammatory cells in mouse lung by flow cytometry.
Results:
We found that miR-454 targeted the 3'-UTR of CXCL12 mRNA to inhibit its protein translation in human lung epithelial cells. Overexpression of miR-454 in mouse lung significantly reduced the LPS-induced increases in permeability index and production of inflammatory cytokines CXCL1, CXCL2, IL6 and TNFα, possibly through suppression of CXCL12/CXCR4-mediated recruitment of inflammatory cells.
Conclusion:
Overexpression of miR-454 in lung may be a promising therapeutic approach to reduce the severity of ALI.
Insights
MicroRNA-454 (miR-454) can inhibit lung inflammation and reduce acute lung injury (ALI) by targeting CXCL12. This study shows miR-454 overexpression is a potential therapy for ALI.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Inflammation Research
Background:
- Acute lung injury (ALI) is a significant human disease with poorly understood pathogenesis and limited therapeutic options.
- Current treatments for ALI have not significantly improved patient outcomes.
- Investigating novel therapeutic targets is crucial for managing ALI.
Purpose of the Study:
- To investigate the potential of microRNAs (miRNAs) in inhibiting ALI-associated lung inflammation.
- To determine if targeting the chemo-attractive factor CXCL12 with miRNAs can reduce ALI severity.
- To explore miR-454 as a therapeutic agent for ALI.
Main Methods:
- Bioinformatics analysis identified miRNAs targeting CXCL12, with functional validation using luciferase reporter assays.
- Adeno-associated virus (AAV) vectors were used to deliver miRNA mimics to mouse lungs for in vivo studies.
- Lipopolysaccharide (LPS) was administered to induce ALI in mice, followed by analysis of lung permeability, inflammatory cytokines, and cell recruitment.
Main Results:
- miR-454 was found to target the 3'-UTR of CXCL12 mRNA, inhibiting its protein translation in human lung epithelial cells.
- Overexpression of miR-454 in mouse lungs significantly reduced LPS-induced increases in lung permeability and inflammatory cytokines (CXCL1, CXCL2, IL6, TNFα).
- These effects are likely mediated by the suppression of CXCL12/CXCR4-dependent inflammatory cell recruitment.
Conclusions:
- Overexpression of miR-454 in the lung presents a promising therapeutic strategy for mitigating ALI.
- Targeting the CXCL12 pathway with miR-454 offers a novel approach to reduce ALI severity.
- Further research into miR-454-based therapies could lead to improved clinical outcomes for ALI patients.
