斯坦尼奥卡尔-1通过JNK激活促进PARP1-依赖的细胞死亡在结肠炎中
Liguo Zhu1, Zhuo Xie1, Guang Yang2
1Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 13, 2023
概括
斯坦尼奥卡尔-1 (STC1) 通过促进细胞死亡途径帕尔塔纳托斯 (parthanatos) 来恶化结肠炎. STC1与PARP1相互作用,激活JNK信号,并在克罗恩病中增加炎症.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 斯坦尼奥卡尔-1 (STC1) 与炎症和氧化应激有关.
- 帕尔塔纳托斯是一种依赖于PARP1激活的编程死细胞死亡途径.
- 对于STC1在结肠炎和腹腔炎中的作用尚不清楚.
研究的目的:
- 为了研究STC1在结肠炎和压力诱导的腹腔炎中的功能.
- 阐明STC1在炎症和细胞死亡中的作用背后的分子机制.
主要方法:
- 在人类克罗恩病 (CD) 患者和小鼠结肠炎模型中分析STC1表达.
- 在STC1淘汰赛和过度表达模型中评估腹腔炎的严重程度和细胞因子表达.
- 共同免疫沉,质谱和蛋白质组分析以确定STC1相互作用伙伴.
- 抑制PARP1和JNK通路的作用.
- 腺相关病毒介导的基因恢复和过度表达.
主要成果:
- 在CD患者和大肠炎模型的炎症结肠粘膜中,STC1的表达显著增加.
- 肠特异性STC1淘汰赛小鼠对DSS诱导的大肠炎具有抗性,显示疾病严重程度降低.
- 过度表达STC1增强了甲状腺和促炎性细胞因子的表达,而STC1淘汰则减少了它们.
- STC1与PARP1相互作用,激活了JNK通路.
- 抑制PARP1和JNK可以缓解STC1诱导的甲状腺炎和炎症.
- 恢复或过度表达STC1和PARP1会加剧DSS诱导的大肠炎.
结论:
- 在大肠炎中,STC1通过STC1-PARP1-JNK通路加剧炎症和腹腔炎.
- 通过调解氧化应激诱导的细胞死亡和炎症,STC1在克罗恩病的发病过程中发挥着关键作用.
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