Klf9在心肌细胞的GR依赖性代谢适应中发挥着关键作用
Chandni Thakkar1, Saleena Alikunju1, Nandita Niranjan1
1From the Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States of America.
葡萄糖皮质体受体 (GR) 的激活通过克鲁佩尔样因子9 (Klf9) 调节心肌细胞代谢. 这种前信号通过日间代谢适应来维持细胞平衡.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 通过葡萄糖皮质体受体 (GR) 激活,葡萄糖皮质体对应激期间的细胞平衡至关重要.
- 在心肌细胞中用德克萨米他 (Dex) 治疗显示出早期的转录因子调节,随后是下游通路基因变化.
研究的目的:
- 调查克鲁佩尔类因子9 (Klf9) 的作用,早期的GR标,在调解葡萄糖皮质体对心肌细胞功能影响中的作用.
- 阐明Klf9依赖的信号通路在调节心肌细胞内的代谢适应.
主要方法:
- 基因组GR结合和转录组分析在用德克萨米治疗的心肌细胞中.
- Klf9染色体免疫沉测序 (ChIP-seq) 用于识别Klf9结合标.
- 使用siRNA和随后的转录组和代谢功能分析 (糖解和线粒应激试验) 的Klf9淘汰实验.
主要成果:
- 德克斯治疗导致Klf9对2150个基因的结合增加.
- Klf9敲击逆转了Dex治疗心肌细胞中1777个不同调节基因中的1640个基因的表达.
- Klf9敲击抑制了德克斯诱导的糖解和线粒体储备呼吸能力的增加.
结论:
- 循环,白天的葡萄糖皮质体受体 (GR) 激活,由Klf9依赖的前信号传导,对于维持心肌细胞细胞平衡至关重要.
- Klf9在调节代谢适应方面发挥着关键作用,包括糖解和氧化酸化,以响应葡萄糖皮质体信号.
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