通过依赖HIF-1α的糖解路径,PTGES参与了肌纤维细胞分化
Min-Hsi Lin1, Yi-Chen Lee2, Jia-Bin Liao3
1Division of Chest Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Journal of cellular and molecular medicine
|October 17, 2024
概括
前列腺素E合成酶 (PTGES) 通过激活依赖HIF-1α的糖解来驱动肺纤维化中的肌纤维细胞分化. 针对PTGES可能为纤维化肺部疾病和相关的肺癌风险提供治疗策略.
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:
- 肺癌是癌症死亡的主要原因,预后不佳.
- 异形性肺纤维化 (IPF) 和慢性阻塞性肺病 (COPD) 会增加肺癌的风险.
- 肌纤维细胞在喘,COPD和IPF等肺部疾病中驱动纤维化.
研究的目的:
- 调查新陈代谢重编程在肺纤维化中的作用.
- 确定参与肌纤维细胞分化的关键分子通路.
- 探索PTGES作为纤维化肺部疾病的潜在治疗点.
主要方法:
- 对肺纤维细胞的基因表达微阵列分析.
- 用细胞因子 (IL-4,IL-13,TNF-α) 治疗肺纤维细胞.
- 在体内肺纤维化的老鼠模型.
- 药理上抑制HIF-1α和糖解.
主要成果:
- 在肺纤维细胞中对脂质代谢途径和PTGES的升调.
- PTGES增加了α-SMA水平,促进了纤维细胞迁移和入侵.
- PTGES激活了AKT酸化和HIF-1α-糖解路径.
- 抑制PTGES或其下游信号减少α-SMA表达.
结论:
- 通过依赖HIF-1α的糖解,PTGES促进肌纤维细胞分化.
- 在肺纤维化模型中,PTGES被上调.
- 针对PTGES和PGE2信号可能是肺纤维化治疗的治疗策略.
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