在Kawasaki病和儿童多系统炎症综合征中的内皮细胞反应
Jihoon Kim1,2, Chisato Shimizu3, Ming He4
1Department of Biomedical Informatics, University of California, San Diego, CA 92093, USA.
International journal of molecular sciences
|August 12, 2023
概括
儿童多系统炎症综合征 (MIS-C) 和川崎病 (KD) 不同地影响内皮细胞 (EC). 在EC中,MIS-C对支持生存的途径进行上调,而KD影响EC恒温并促进过渡,这可能解释了各种心血管结果.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 儿童心脏病学 儿童心脏病学
背景情况:
- 川崎病 (KD) 和儿童多系统炎症综合征 (MIS-C) 是儿科炎症状况,症状重叠,但心血管结果不同.
- 内皮细胞 (ECs) 在心血管健康中起着至关重要的作用,在KD和MIS-C中可能会受到不同的影响,导致不同的临床轨迹.
研究的目的:
- 研究暴露于MIS-C患者血清的内皮细胞 (ECs) 的不同分子反应,与KD相比.
- 确定EC中的特定基因表达模式和途径,将MIS-C与KD区分开来,可能解释心血管并发症的差异.
主要方法:
- 进行RNA测序 (RNA-seq) 在培养的人类EC上进行,这些EC与MIS-C,KD和健康对照队伍的预处理血清进行化.
- 使用权重基因共同表达网络分析 (WGCNA) 和差异基因表达分析来确定关键的分子通路和转录.
主要成果:
- 在EC中,MIS-C血清诱导了TNFα/NFκB通路基因,支持生存的转录和与自相关的基因 (UBD,EBI3,SQSTM1) 的显著上调.
- 相反,与MIS-C.相比,KD血清与降低EC稳态和内皮-介质细胞过渡 (EndoMT) 相关的转录有关.
- 在MIS-C中,WGCNA确定了七个不同的基因模块,突出显示了改变的免疫反应,EC平衡和EndoMT.
结论:
- 当暴露于MIS-C与KD血清时,内皮细胞表现出明显的转录组形状,其特征在于MIS-C中增加了亲生存信号.
- 观察到的EC反应的差异,包括改变的平衡和EndoMT,可能是MIS-C和KD观察到的不同心血管后续的基础.
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