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<p>Cellular senescence (CS) is recognized as a critical driver of aging and age-related disorders. Recent studies have emphasized the roles of ion channels as key mediators of CS. Nonetheless, the roles and regulatory mechanisms of chloride intracellular channels (CLICs) during CS remain largely unexplored. In this study, we conducted RNA sequencing on bleomycin-induced senescent lung tissues from mice and identified <i>Clic3</i> as the most significantly upregulated <i>CLIC</i> member. Furthermore, our findings revealed that the knockdown of CLIC3 mitigated intracellular chloride ion lose, mitochondrial dysfunction, nuclear enlargement, DNA damage, CS progression, and expression of senescence-associated secretory phenotype (SASP) triggered by bleomycin. Mechanistically, CLIC3 controls CS by translocating to the membrane where it interacts with extracellular signal-regulated kinase 7 (ERK7). Overall, our work demonstrates that the chloride intracellular channel CLIC3 modulates CS by repressing ERK7 activity and provides novel insights into the role of chloride channels.</p>

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Chloride intracellular channel CLIC3 mediates fibroblast cellular senescence by interacting with ERK7

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月14日

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  • Changjiao Luan,
  • Yue Gao,
  • Jun Zhao,
  • Xiaohui Zhang,
  • Chaofan Wang,
  • Wentao Sun,
  • Yucheng Li,
  • Xinxing Yang,
  • Jiaxiao Chen,
  • Weili Liu,
  • Weijuan Gong,
  • Xingjie Ma

摘要

Cellular senescence (CS) is recognized as a critical driver of aging and age-related disorders. Recent studies have emphasized the roles of ion channels as key mediators of CS. Nonetheless, the roles and regulatory mechanisms of chloride intracellular channels (CLICs) during CS remain largely unexplored. In this study, we conducted RNA sequencing on bleomycin-induced senescent lung tissues from mice and identified Clic3 as the most significantly upregulated CLIC member. Furthermore, our findings revealed that the knockdown of CLIC3 mitigated intracellular chloride ion lose, mitochondrial dysfunction, nuclear enlargement, DNA damage, CS progression, and expression of senescence-associated secretory phenotype (SASP) triggered by bleomycin. Mechanistically, CLIC3 controls CS by translocating to the membrane where it interacts with extracellular signal-regulated kinase 7 (ERK7). Overall, our work demonstrates that the chloride intracellular channel CLIC3 modulates CS by repressing ERK7 activity and provides novel insights into the role of chloride channels.