Related Experiment Video
Updated: Jan 11, 2026
Bronchoalveolar Lavage Exosomes in Lipopolysaccharide-induced Septic Lung Injury
Published on: May 21, 2018
Exosomal miR-132-3p derived from M1 macrophages mediates diffuse alveolar haemorrhage in systemic lupus erythematosus
1Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Objective:
This study examines how exosomal miR-132-3p from M1 macrophages contributes to the development of SLE-associated diffuse alveolar haemorrhage (SLE-DAH) and the molecular mechanisms involved.
Methods:
A pristane-induced murine model of SLE-DAH was established, and mice received either a miR-132-3p antagomir or control. Parallel in vitro studies were conducted using human alveolar epithelial (A549) and human pulmonary microvascular endothelial cells (HPMECs) undergoing treatment with either miR-132-3p mimics or inhibitors. Barrier integrity, inflammation, apoptosis and molecular signalling were evaluated using real-time PCR (qRT-PCR), western blotting, immunofluorescence, transepithelial electrical resistance (TEER) measurement, FITC-dextran permeability, TUNEL assay and dual-luciferase assays.
Results:
Compared with controls, pristane-induced SLE-DAH mice exhibited pronounced pulmonary haemorrhage, lung weight gain and alveolar damage, along with elevated inflammation-related cytokines (IL-6, TNF-α, IL-1β) and decreased immune-regulating mediators (IL-10, TGF-β) in bronchoalveolar lavage fluid; these changes were alleviated by miR-132-3p antagomir. miR-132-3p was upregulated in M1 macrophages, exosomes, and recipient A549 and HPMEC cells in both models, and suppressed by antagomir or inhibitor. Its overexpression impaired barrier integrity by downregulating ZO-1, Occludin and E-cadherin, TEER, enhanced FITC-dextran permeability and promoted apoptosis; all were reversed upon miR-132-3p inhibition. Meanwhile, SIRT1 was suppressed and NF-κB p65 and IκBα phosphorylation enhanced, with dual-luciferase assays confirming the direct interaction between miR-132-3p and SIRT1.
Conclusion:
M1 macrophage-originated exosomal miR-132-3p promotes lung injury in SLE-associated DAH by impairing alveolar barrier integrity and enhancing inflammatory signalling via the SIRT1/NF-κB axis. Targeting miR-132-3p could offer a novel treatment option for SLE-DAH.
Insights
Exosomal miR-132-3p from M1 macrophages drives lung injury in systemic lupus erythematosus (SLE)-associated diffuse alveolar hemorrhage (DAH). Targeting this microRNA offers a potential new therapy for SLE-DAH.
Area of Science:
- Immunology
- Molecular Biology
- Pulmonary Medicine
Background:
- Systemic lupus erythematosus (SLE) can lead to diffuse alveolar hemorrhage (DAH), a severe pulmonary complication.
- The role of specific microRNAs, such as miR-132-3p, in SLE-DAH pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the contribution of exosomal miR-132-3p derived from M1 macrophages to SLE-associated DAH.
- To elucidate the underlying molecular mechanisms, including its impact on alveolar barrier integrity and inflammatory signaling.
Main Methods:
- Established a pristane-induced murine model of SLE-DAH.
- Utilized in vitro studies with human alveolar epithelial cells (A549) and pulmonary microvascular endothelial cells (HPMECs).
- Administered miR-132-3p antagomirs/inhibitors or mimics and assessed barrier function, inflammation, and apoptosis via molecular and cellular assays.
Main Results:
- Pristane-induced SLE-DAH mice showed lung injury, inflammation, and altered cytokine profiles, which were ameliorated by miR-132-3p antagomir.
- Exosomal miR-132-3p was upregulated and contributed to impaired alveolar barrier integrity, increased permeability, and apoptosis.
- miR-132-3p directly targeted SIRT1, suppressing it and activating the NF-κB signaling pathway.
Conclusions:
- Exosomal miR-132-3p from M1 macrophages exacerbates lung injury in SLE-DAH by disrupting alveolar barrier integrity and promoting inflammation via the SIRT1/NF-κB pathway.
- Inhibition of miR-132-3p presents a promising therapeutic strategy for SLE-associated DAH.
