Scholarlink

<p>Defective alveolar re-epithelialization following acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represents a critical barrier to clinical recovery. Intrinsic signals that could be harnessed to speed this repair remain poorly defined. Endogenous electric fields (EFs) arise immediately after epithelial injury and are recognized as mediators of cell migration and morphogenesis, but their impact on lung epithelial proliferation is unknown. Here we demonstrate that physiological-strength direct-current EFs (100–200 mV/mm) are potent pro-mitogenic signals for both human bronchial (BEAS-2B) and murine alveolar (MLE-12) epithelial cells. Within a custom live-cell electrotactic chamber, EFs exposure for 4&#xa0;h doubled EdU incorporation, increased Ki-67 expression, and elevated real-time mitotic events without altering spindle orientation. RNA-seq analysis of BEAS-2B cells with EFs exposure identified 1,447 differentially expressed genes, with significant enrichment of the PI3K/AKT signaling pathway and immunoblotting further confirmed rapid phosphorylation of PI3K p85 (Tyr458)/p55 (Tyr199) and AKT (Ser473). Selective inhibition with Alpelisib or LY294002 abolished pathway activation and fully suppressed the pro-proliferative effect of EFs. Furthermore, EFs triggered AKT-dependent phosphorylation of glycogen synthase kinase-3β (GSK3β) at Ser9, while blockade with the GSK3β inhibitor Tideglusib or upstream PI3K inhibitors suppressed this event and attenuated EF-induced proliferation. Taken together, our findings delineate the PI3K/AKT/GSK3β signaling axis through which EFs enhance pulmonary epithelial proliferation. This work identifies physiological EFs as previously unrecognized regenerative cues in the lung and underscores bioelectric modulation as a promising therapeutic strategy to accelerate alveolar repair in ALI/ARDS.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Bioelectric fields drive pulmonary epithelial proliferation through PI3K/AKT/GSK3β signaling

  • 期刊论文

  • 发表日期：

    2026年1月29日

查看全文
  • Chenjun Shi,
  • Conghua Lu,
  • Caiyu Lin,
  • Shaopan Lian,
  • Huanyu Luo,
  • Ziyin You,
  • Li Li

摘要

Defective alveolar re-epithelialization following acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represents a critical barrier to clinical recovery. Intrinsic signals that could be harnessed to speed this repair remain poorly defined. Endogenous electric fields (EFs) arise immediately after epithelial injury and are recognized as mediators of cell migration and morphogenesis, but their impact on lung epithelial proliferation is unknown. Here we demonstrate that physiological-strength direct-current EFs (100–200 mV/mm) are potent pro-mitogenic signals for both human bronchial (BEAS-2B) and murine alveolar (MLE-12) epithelial cells. Within a custom live-cell electrotactic chamber, EFs exposure for 4 h doubled EdU incorporation, increased Ki-67 expression, and elevated real-time mitotic events without altering spindle orientation. RNA-seq analysis of BEAS-2B cells with EFs exposure identified 1,447 differentially expressed genes, with significant enrichment of the PI3K/AKT signaling pathway and immunoblotting further confirmed rapid phosphorylation of PI3K p85 (Tyr458)/p55 (Tyr199) and AKT (Ser473). Selective inhibition with Alpelisib or LY294002 abolished pathway activation and fully suppressed the pro-proliferative effect of EFs. Furthermore, EFs triggered AKT-dependent phosphorylation of glycogen synthase kinase-3β (GSK3β) at Ser9, while blockade with the GSK3β inhibitor Tideglusib or upstream PI3K inhibitors suppressed this event and attenuated EF-induced proliferation. Taken together, our findings delineate the PI3K/AKT/GSK3β signaling axis through which EFs enhance pulmonary epithelial proliferation. This work identifies physiological EFs as previously unrecognized regenerative cues in the lung and underscores bioelectric modulation as a promising therapeutic strategy to accelerate alveolar repair in ALI/ARDS.