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<p>Asthma is a classical inflammation-related disease, and its pathogenesis is closely associated with mitochondrial dysfunction and mitophagy. Although Anemoside B4 (AmB4) exhibits anti‑inflammatory properties in various diseases, its role in regulating mitochondrial dysfunction-related mitophagy in asthma remains unknown. In vivo and in vitro asthma models were constructed using house dust mite (HDM)-stimulated BALB/c mice and HDM-treated BEAS-2B cells. Hematoxylin and eosin and periodic acid–Schiff staining were used for the pathological examination of lung tissues. Mitophagy-related proteins were assessed by Western blotting and immunofluorescence. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were measured using JC-1 and DCFH‑DA assays, respectively. Mitochondria was observed by transmission electron microscopy. Cytokine concentrations were determined by ELISA. The mito‑Keima reporter was employed to directly quantify mitophagy and analyzed by flow cytometry. The effect of KAT2B on IRF3 protein stability was determined by cycloheximide chase assay. The ubiquitination of IRF3 was assessed by immunoprecipitation. Intermolecular interactions were analyzed using co-immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. The results illuminated AmB4 alleviated asthma by downregulating KAT2B expression, thereby ameliorating mitochondrial dysfunction and suppressing mitophagy in vivo. Furthermore, AmB4 increased the MMP of BEAS-2B cells and reduced levels of ROS, LC3B, and Tomm20 via KAT2B inhibition. Mechanistically, KAT2B promoted the lysine acetylation of interferon regulatory factor 3 (IRF3) at K315, and IRF3 enhanced PTEN-induced putative kinase 1 (PINK1) expression by binding to its promoter. Additionally, AmB4 inhibited mitochondrial dysfunction-related mitophagy by targeting the KAT2B/IRF3/PINK1 axis, thereby alleviating asthma. Specifically, AmB4 suppressed IRF3-mediated PINK1 transcription by inhibiting KAT2B-dependent acetylation of IRF3 at K315, thereby ameliorating mitochondrial dysfunction and suppressing mitophagy, which ultimately improved asthma symptoms.</p>

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Anemoside B4 inhibits mitochondrial dysfunction-related mitophagy in asthma by regulating KAT2B/IRF3 axis

  • 期刊论文

  • 发表日期：

    2026年6月2日

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  • Hao Tang,
  • Ping Li,
  • Mingxia Shang,
  • Zhiping Zhou,
  • Xing Yang,
  • Bin Liu

摘要

Asthma is a classical inflammation-related disease, and its pathogenesis is closely associated with mitochondrial dysfunction and mitophagy. Although Anemoside B4 (AmB4) exhibits anti‑inflammatory properties in various diseases, its role in regulating mitochondrial dysfunction-related mitophagy in asthma remains unknown. In vivo and in vitro asthma models were constructed using house dust mite (HDM)-stimulated BALB/c mice and HDM-treated BEAS-2B cells. Hematoxylin and eosin and periodic acid–Schiff staining were used for the pathological examination of lung tissues. Mitophagy-related proteins were assessed by Western blotting and immunofluorescence. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were measured using JC-1 and DCFH‑DA assays, respectively. Mitochondria was observed by transmission electron microscopy. Cytokine concentrations were determined by ELISA. The mito‑Keima reporter was employed to directly quantify mitophagy and analyzed by flow cytometry. The effect of KAT2B on IRF3 protein stability was determined by cycloheximide chase assay. The ubiquitination of IRF3 was assessed by immunoprecipitation. Intermolecular interactions were analyzed using co-immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. The results illuminated AmB4 alleviated asthma by downregulating KAT2B expression, thereby ameliorating mitochondrial dysfunction and suppressing mitophagy in vivo. Furthermore, AmB4 increased the MMP of BEAS-2B cells and reduced levels of ROS, LC3B, and Tomm20 via KAT2B inhibition. Mechanistically, KAT2B promoted the lysine acetylation of interferon regulatory factor 3 (IRF3) at K315, and IRF3 enhanced PTEN-induced putative kinase 1 (PINK1) expression by binding to its promoter. Additionally, AmB4 inhibited mitochondrial dysfunction-related mitophagy by targeting the KAT2B/IRF3/PINK1 axis, thereby alleviating asthma. Specifically, AmB4 suppressed IRF3-mediated PINK1 transcription by inhibiting KAT2B-dependent acetylation of IRF3 at K315, thereby ameliorating mitochondrial dysfunction and suppressing mitophagy, which ultimately improved asthma symptoms.