在人类肺纤维细胞中,C/EBPβ/STAT3/AP-1转录复合体形成在血栓诱导的结缔组织生长因子表达中的作用
Hung-Sheng Hua1, Yi-Ting Huang2, Hong-Sheng Lee1
1Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Chen Wei-Tien Research Center of Thoracic Medicine, Taipei Medical University, Taipei, Taiwan.
European journal of pharmacology
|September 19, 2025
概括
热血素通过PI3K/Akt路径激活CCAAT/增强剂结合蛋白β (C/EBPβ),推动结合组织生长因子 (CTGF) 的产生. 这种C/EBPβ/STAT3/AP-1复合体对于异常性肺纤维化进展至关重要,并具有潜在的治疗标.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 肺部医学 肺部医学
背景情况:
- 异形性肺纤维化 (IPF) 是一种渐进的肺部疾病.
- CCAAT/增强剂结合蛋白β (C/EBPβ) 与IPF的进展有关.
- 肺纤维细胞中结合血栓,C/EBPβ,STAT3,AP-1和CTGF的确切机制尚不清楚.
研究的目的:
- 阐明血栓通过人类肺纤维细胞中的C/EBPβ/STAT3/AP-1转录复合体调节结合组织生长因子 (CTGF) 生产的机制.
- 研究PI3K/Akt路径在血栓诱导的C/EBPβ激活和CTGF产生中的作用.
- 评估这些途径在白血素诱导的肺纤维化模型中的相关性.
主要方法:
- 在人类肺纤维细胞中进行的C/EBPβ淘汰实验 (WI-38).
- 路西法酶记者测试测量CTGF和转录复合体活动.
- 西部涂抹以评估蛋白质酸化和转位.
- 信号通路的药理性抑制 (PI3K/Akt,JNK,JAK2). 这种药物可以
- 从白素诱导的肺纤维化模型中分析肺组织.
主要成果:
- 血激素刺激增强了C/EBPβ酸化,核转位和CTGF的产生.
- C/EBPβ敲击抑制了由血栓诱导的CTGF产生和STAT3和AP-1的转录活性.
- PI3K/Akt路径调解了由血栓诱导的C/EBPβ激活和CTGF的产生.
- 在白素诱导的纤维化中,观察到酸化的C/EBPβ,STAT3和c-Jun,以及升高的C/EBPβ和CTGF蛋白水平.
结论:
- 热血素通过PI3K/Akt路径激活C/EBPβ,从而导致CTGF在肺纤维细胞中的诱导.
- 这种C/EBPβ/STAT3/AP-1复合体对于以血栓为媒介的CTGF产生至关重要.
- C/EBPβ上调和C/EBPβ/STAT3/AP-1复合体的形成与肺纤维化病原体有关,并代表潜在的治疗点.
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