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Serum Exosome-Derived MiR-7 Exacerbates Chronic Obstructive Pulmonary Disease by Regulating Macrophage
Yiming Jiang1, Jinhai Wang1, He Zhang1
1Department of Emergency, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China.
Background:
Polarization of macrophages and miR-7 have been reported to greatly influence the progress of chronic obstructive pulmonary disease (COPD). However, the interaction is unclear. We aimed to investigate the role of miR-7 in the serum exosome of COPD, thus further revealing the underlying mechanism of COPD.
Methods:
The study was conducted in 2022 in The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China. COPD mouse model was established. Macrophages were sorted by flow cytometry assay. ELISA kits were used to detect the levels of TNF-α and IL-6. Exosomes were identified by confocal microscopy and PKH67 staining. RT-qPCR and western blot assay were performed to determine the mRNA and protein expressions. H&E staining assay was used to assess the tissue injury. CCK-8 assay was applied to evaluate cell viability. Luciferase reporter assay was used to confirm the binding between PIM1 and miR-7.
Results:
The exosomes derived from the COPD mice serum exerted high level of miR-7, which induced M1 differentiation of macrophages and increased the secretion of proinflammatory factors in vivo and in vitro. The effects of exosomes from COPD mice could be inhibited by miR-7 inhibitor. Bioinformatic prediction, luciferase reporter assay, and western blot assay showed an interaction between miR-7 and PIM1. Further examination showed that miR-7 regulated macrophage activation and differentiation to M1 via PIM1 in vitro.
Conclusion:
miR-7 from serum exosomes might exacerbate COPD by stimulating macrophage differentiation to M1, supplying a potential therapeutic target for COPD treatment.
Insights
MicroRNA-7 (miR-7) in serum exosomes exacerbates chronic obstructive pulmonary disease (COPD) by promoting M1 macrophage polarization. This finding offers a potential therapeutic target for COPD treatment.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Immunology
Background:
- Macrophage polarization and microRNA-7 (miR-7) are implicated in chronic obstructive pulmonary disease (COPD) progression.
- The precise interaction between miR-7 and macrophage polarization in COPD remains unclear.
Purpose of the Study:
- To investigate the role of miR-7 within serum exosomes in COPD.
- To elucidate the underlying mechanisms of COPD pathogenesis involving miR-7.
Main Methods:
- Established a COPD mouse model and sorted macrophages.
- Quantified inflammatory factors (TNF-α, IL-6) and miR-7 levels in exosomes.
- Utilized RT-qPCR, Western blot, and H&E staining for molecular and tissue analysis.
- Confirmed the interaction between miR-7 and PIM1 using luciferase reporter assays.
Main Results:
- Serum exosomes from COPD mice showed elevated miR-7 levels.
- High miR-7 levels induced M1 macrophage differentiation and increased pro-inflammatory cytokine secretion.
- miR-7 inhibition reversed these effects.
- miR-7 directly targets PIM1, regulating macrophage activation and M1 differentiation.
Conclusions:
- miR-7 in serum exosomes exacerbates COPD by promoting M1 macrophage polarization.
- Targeting miR-7 presents a potential therapeutic strategy for COPD.
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