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全球转录组分析揭示了内皮对TNF反应的不同阶段

Eike C Struck¹, Tatiana Belova², Ping-Han Hsieh²

¹Department of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway.

Journal of immunology (Baltimore, Md. : 1950)

|November 29, 2023

概括

瘤坏死因子-α (TNF-α) 在人类内皮细胞 (ECs) 中触发了不同的基因表达阶段. 这项研究揭示了对TNF-α的急性和晚期转录反应,为炎症和向治疗提供了洞察力.

科学领域:

分子生物学分子生物学
免疫学免疫学免疫学
细胞生物学细胞生物学

背景情况:

血管内皮是调节血液和组织交换的关键接口.
瘤坏死因子-α (TNF-α) 是一个关键的炎症媒介,影响内皮细胞 (EC) 功能.
对TNF-α的EC转录反应的时间动态需要进一步阐明.

研究的目的:

综合分析人类EC对TNF-α的时间循环转录反应.
在TNF-α刺激后在EC中识别不同的时间阶段和基因表达模式.
为了研究对TNF-α的EC反应的基于性别的差异.

主要方法:

用TNF-α刺激的人类EC的延长时间分析 (30分钟至72小时).
调节基因的识别和权重基因网络的相关性分析.
对基因表达数据的基于性别的子集分析.

主要成果:

确定了对TNF-α的EC转录反应的两个不同的时间阶段:急性阶段 (14小时) 和后期阶段 (1224小时).
在男性和女性EC中,反应是可比的.
急性阶段涉及新基因,而后期阶段则由干扰素刺激基因 (ISG) 主导,独立于 de novo ISG 生产. 此外,TNF-α还抑制了特定基因组的转录.

结论:

该研究阐明了对TNF-α的EC转录反应的全球动态,揭示了不同的急性和晚期阶段.
这些发现突出了炎症期间ECs基因调节的复杂相互作用.
这些数据为了解EC在炎症中的作用和开发TNF向治疗提供了基础.

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