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Updated: Jun 7, 2025
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Macrophage-derived exosomal miR-2137 regulates pyroptosis in LPS-induced acute lung injury
Cong Ye1, Xiaodong Yang1, Lin Zhu2
1Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
Background:
Alveolar macrophages (AMs) play a predominant role in acute lung injury (ALI). However, the role of macrophage-derived exosomal miRNAs in lipopolysaccharide (LPS)-induced ALI has not been determined.
Methods:
We previously reported that exosomes in the bronchoalveolar lavage fluid (BALF) of mice with ALI were derived predominantly from macrophages. Exosomal small RNA sequencing was conducted to identify the miRNA profiles. Exosomes derived from LPS-induced macrophages (LPS-exos) were intravenously administered to C57BL/6J mice, after which lung injury and pyroptosis were assessed. LPS-exos were cultured with alveolar epithelial cells (AECs) to further validate the results of the animal studies.
Results:
LPS-exos promoted lung inflammation and pyroptosis in vivo and in vitro. MiR-2137 was significantly upregulated in both LPS-exos and in MLE-12 cells. LPS-exos reduced cell viability, promoted the expression of LDH and inflammatory cytokines, and exacerbated vacuolization in MLE-12 cells. The administration of miR-2137 mimics and LPS-treated exosomes further strengthened these effects and enhanced pyroptosis mediated by NLRP3, Caspase1, ASC, and GSDMD. MiR-2137 mediated the effects of LPS-exos by targeting Wnt9a in AECs. In addition, the miR-2137 inhibitor markedly decreased the severity of LPS-exo-induced histological lesions, inflammation and pyroptosis in the lung.
Conclusion:
Exosomal miR-2137 derived from AMs contributes to LPS-induced ALI by inducing AEC pyroptosis through the targeting of Wnt9a to activate the Wnt signaling pathway. This study revealed that AMs and AECs interact in ALI, providing novel strategies for ALI treatment.
Insights
Macrophage-derived exosomes carrying miR-2137 worsen acute lung injury (ALI) by promoting alveolar epithelial cell pyroptosis. Inhibiting miR-2137 offers a potential therapeutic strategy for ALI.
Area of Science:
- Immunology
- Cell Biology
- Molecular Medicine
Background:
- Alveolar macrophages (AMs) are crucial in acute lung injury (ALI).
- The specific role of macrophage-derived exosomal microRNAs (miRNAs) in lipopolysaccharide (LPS)-induced ALI remains unclear.
Purpose of the Study:
- To investigate the function of macrophage-derived exosomal miRNAs in LPS-induced ALI.
- To identify specific miRNAs involved in the pathogenesis of ALI and their molecular targets.
Main Methods:
- Exosomes from LPS-induced macrophages (LPS-exos) were isolated and characterized.
- LPS-exos were administered to C57BL/6J mice to assess lung injury and pyroptosis.
- In vitro studies involved culturing LPS-exos with alveolar epithelial cells (AECs).
- Exosomal small RNA sequencing identified differentially expressed miRNAs, focusing on miR-2137.
Main Results:
- LPS-exos significantly promoted lung inflammation and pyroptosis in vivo and in vitro.
- MiR-2137 was notably upregulated in LPS-exos and affected AECs.
- LPS-exos, particularly miR-2137, reduced AEC viability, increased inflammatory markers (LDH, cytokines), and exacerbated pyroptosis via the NLRP3 inflammasome pathway.
- MiR-2137 targeted Wnt9a in AECs, activating the Wnt signaling pathway.
- Inhibition of miR-2137 ameliorated LPS-induced lung injury and pyroptosis.
Conclusions:
- Exosomal miR-2137 from AMs contributes to LPS-induced ALI by triggering AEC pyroptosis via Wnt9a targeting.
- This highlights a critical interaction between AMs and AECs in ALI pathogenesis.
- Targeting exosomal miR-2137 presents a promising therapeutic avenue for ALI treatment.
