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<p>Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality rates, and macrophage polarization is critical for its pathogenesis. Exosomes are crucial inflammation mediators; however, their role and mechanism in LPS-induced ARDS remain unclear. We investigated whether airway epithelial cell-derived exosomes on lipopolysaccharide (LPS)-induced ARDS model regulate macrophage polarization via the GATA1 pathway. Exosomes isolated from PBS- or LPS-treated airway epithelial cells (BEAS-2B) were injected into C57BL/6 wild-type mice intratracheally; macrophage polarization, cytokine secretion, and cell apoptosis were examined. In an in vitro co-culture system, human macrophage precursor (THP-1) was co-cultured with these exosomes to further confirm the results of the in vivo animal study. Bioinformatic analysis and miRNA mimic/inhibitor were used to explore the potential mechanisms involved. LPS-induced exosomes promoted M1 macrophage polarization, cytokine secretion, and cell apoptosis in vivo and in vitro co-culture models. Bioinformatic analysis indicated that miR-301a-3p-mediated LPS-exosomes (LPS-Exo) functioned via targeting the GATA1 downstream pathway in macrophages. Administering miR-301a-3p mimic significantly aggravated LPS-Exo-induced M1 macrophage polarization, cytokine secretion, and cell apoptosis, which were partially reversed by the miR-301a-3p inhibitor. The miR-301a-3p mediated LPS-Exo function via upregulating the GATA1/NF‑κB and downregulating GATA1/Akt pathways in macrophages. Exosomal miR-301a-3p derived from airway epithelial cells aggravates ARDS development via promoting M1 macrophage polarization, inflammatory response, and lung injury via regulating the GATA1 pathway.</p>

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Exosomal miR‑301a‑3p of airway epithelial cells regulates macrophage polarization and promotes lung injury via GATA1 pathway in acute respiratory distress syndrome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月19日

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  • Jing Gao,
  • Xiao Yu,
  • Xiangmei Li,
  • Shilong Zhao,
  • Mengying Yao,
  • Xiaoxiao Lu

摘要

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality rates, and macrophage polarization is critical for its pathogenesis. Exosomes are crucial inflammation mediators; however, their role and mechanism in LPS-induced ARDS remain unclear. We investigated whether airway epithelial cell-derived exosomes on lipopolysaccharide (LPS)-induced ARDS model regulate macrophage polarization via the GATA1 pathway. Exosomes isolated from PBS- or LPS-treated airway epithelial cells (BEAS-2B) were injected into C57BL/6 wild-type mice intratracheally; macrophage polarization, cytokine secretion, and cell apoptosis were examined. In an in vitro co-culture system, human macrophage precursor (THP-1) was co-cultured with these exosomes to further confirm the results of the in vivo animal study. Bioinformatic analysis and miRNA mimic/inhibitor were used to explore the potential mechanisms involved. LPS-induced exosomes promoted M1 macrophage polarization, cytokine secretion, and cell apoptosis in vivo and in vitro co-culture models. Bioinformatic analysis indicated that miR-301a-3p-mediated LPS-exosomes (LPS-Exo) functioned via targeting the GATA1 downstream pathway in macrophages. Administering miR-301a-3p mimic significantly aggravated LPS-Exo-induced M1 macrophage polarization, cytokine secretion, and cell apoptosis, which were partially reversed by the miR-301a-3p inhibitor. The miR-301a-3p mediated LPS-Exo function via upregulating the GATA1/NF‑κB and downregulating GATA1/Akt pathways in macrophages. Exosomal miR-301a-3p derived from airway epithelial cells aggravates ARDS development via promoting M1 macrophage polarization, inflammatory response, and lung injury via regulating the GATA1 pathway.