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<p>Caveolin-1 (CAV1), a pivotal protein implicated in endothelial cell-mediated angiogenesis, assumes an ambiguous role with elusive underlying mechanisms in the pathogenesis of inflammatory bowel disease (IBD). In this investigation, we delineated the involvement of CAV1 in murine models of dextran sulfate sodium (DSS)-induced colitis. CAV1 knockout mice manifested attenuated pathological and inflammatory damage to the epithelium, whereas mice overexpressing CAV1 exhibited contrasting outcomes. In vivo, the accumulation of epithelial CAV1 contributed to the disruption of the epithelial barrier by promoting necroptosis. Subsequent mechanistic analyses revealed that the colitis-protective protein DJ-1 regulated CAV1 through a proteasome-mediated protein degradation pathway. Utilizing necroptosis-modeled organoids from murine intestines and pharmacological inhibition of necroptosis, our findings demonstrated that the DJ-1/CAV1 pathway governed epithelial inflammation via necroptosis in the context of colitis. In summary, our research revealed that epithelial CAV1 aggravated necroptosis in experimental colitis, leading to impairment of the epithelial barrier, which was negatively regulated by DJ-1.</p><p></p>

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DJ-1 counteracts Caveolin-1-mediated necroptosis to inhibit epithelial barrier dysfunction in colitis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月29日

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  • Mengli Yu,
  • Jie Zhang,
  • Bingru Lin,
  • Wei Zhu,
  • Xin Song,
  • Jiaqi Pan,
  • Dingwu Li,
  • Xinjue He,
  • Jing Sun,
  • Zhe Shen,
  • Chaohui Yu

摘要

Caveolin-1 (CAV1), a pivotal protein implicated in endothelial cell-mediated angiogenesis, assumes an ambiguous role with elusive underlying mechanisms in the pathogenesis of inflammatory bowel disease (IBD). In this investigation, we delineated the involvement of CAV1 in murine models of dextran sulfate sodium (DSS)-induced colitis. CAV1 knockout mice manifested attenuated pathological and inflammatory damage to the epithelium, whereas mice overexpressing CAV1 exhibited contrasting outcomes. In vivo, the accumulation of epithelial CAV1 contributed to the disruption of the epithelial barrier by promoting necroptosis. Subsequent mechanistic analyses revealed that the colitis-protective protein DJ-1 regulated CAV1 through a proteasome-mediated protein degradation pathway. Utilizing necroptosis-modeled organoids from murine intestines and pharmacological inhibition of necroptosis, our findings demonstrated that the DJ-1/CAV1 pathway governed epithelial inflammation via necroptosis in the context of colitis. In summary, our research revealed that epithelial CAV1 aggravated necroptosis in experimental colitis, leading to impairment of the epithelial barrier, which was negatively regulated by DJ-1.