Platelet-Derived Exosomal miR-142-3p Inhibits Macrophage M1 Polarization and PANoptosis to Alleviate Acute Lung Injury via the MAPK Pathway.

Authors

Man Zhao, Quanzhao He, Ziyuan Wang, Shirui Xu, Senhao Wei, Linke Zhang, Wanfeng Jin, Qiang Zhang, Yang Yu, Yuxin Leng, Qinggang Ge

Published in

ACS applied materials & interfaces. Jul 24, 2026. Epub Jul 24, 2026.

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an acute, life-threatening form of pulmonary disease characterized by systemic inflammation, for which current treatments are not sufficiently effective. Platelet-derived exosomes (PLT-exos) are noted for their specific targeting ability to inflammatory sites, minimal immunogenicity, and positive anti-inflammatory effects, positioning them as a promising therapeutic candidate. However, the specific effects and mechanisms of PLT-exos in ALI/ARDS remain poorly understood. Here, utilizing a lipopolysaccharide (LPS)-induced ALI model in murine and cell models, we first demonstrated that activated platelet-derived exosomes (AP-exos) are preferentially taken up by lung macrophages, leading to suppressed macrophage M1 polarization and PANoptosis and reduced lung inflammation and injury, which were closely linked to the inhibition of MAPK pathway activity. Mechanistically, the protective effects of AP-exos were partially mediated by the highly enriched miR-142-3p, as evidenced by the intervention with miR-142-3p significantly inhibiting their protective effect against LPS-induced ALI injury in mice. Furthermore, we noted a negative correlation between the level of miR-142-3p derived from plasma exosomes and the severity of ARDS, suggesting its potential in predicting the severity of ARDS. Further investigation revealed that TMEM120B (T120B) functions as a downstream target of miR-142-3p. Overall, the findings suggested that activated platelets release exosomes that inhibit macrophage M1 polarization and PANoptosis, contributing to the pathogenesis of ARDS via the miR-142-3p/T120B/MAPK axis.

PMID:
42554361
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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