体外肺灌注过程中PANoptosis和Ferroptosis的激活。

Yajin Zhao,Lubiao Liang,Abby McCaig,Tanroop Aujla,Shaf Keshavjee,Mingyao Liu
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引用次数: 0

摘要

最近的一项研究表明,在人肺移植再灌注过程中,PANoptosis相关基因上调。然而,体外肺灌注(EVLP)对不同细胞死亡途径的影响及其与炎症基因和临床特征的关系尚不清楚。我们对49例脑死亡(DBD)和39例循环死亡(DCD)肺捐赠的evlp前和evlp后的活检进行了转录组学分析。采用基因集富集分析(GSEA)和单样本GSEA (ssGSEA)来评估细胞死亡和炎症途径的富集情况。我们进一步探讨了这些途径、供体特征和临床结果之间的关系。与DCD肺相比,DBD肺细胞凋亡和铁下垂基因组明显富集。在EVLP期间,在DBD和DCD供体肺中,焦亡、凋亡、坏死和铁亡基因组均显著上调,并与炎症途径密切相关。供体年龄、性别和吸烟史与特定的细胞死亡途径有关。在DCD肺中,铁中毒相关基因的表达与受体早期预后相关。总之,细胞死亡基因组的表达是供型特异性的。EVLP过程中多细胞死亡和炎症途径的识别为改善供体肺质量和提高临床结果提供了潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Activation of PANoptosis and Ferroptosis during Ex Vivo Lung Perfusion in Human Lungs.
A recent study demonstrated upregulation of PANoptosis related genes during reperfusion in human lung transplants. However, the impact of ex vivo lung perfusion (EVLP) on different cell death pathways and their relationship with inflammatory genes and clinical characteristics remains unknown. We conducted transcriptomic analyses on pre- and post-EVLP biopsies from 49 donation after brain death (DBD) and 39 donation after circulatory death (DCD) lungs. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to assess the enrichment of cell death and inflammatory pathways. We further explored the relationships between these pathways, donor characteristics, and clinical outcomes. DBD lungs showed significant enrichment of apoptosis and ferroptosis gene sets compared to DCD lungs. During EVLP, pyroptosis, apoptosis, necroptosis, and ferroptosis gene sets were significantly upregulated and strongly correlated with inflammatory pathways in both DBD and DCD donor lungs. Donor age, sex and smoking history were associated with specific cell death pathways. In DCD lungs, the expression of ferroptosis-related genes was associated with recipient early outcomes. In conclusion, the expression of cell death gene sets is donor-type specific. The identification of multiple cell death and inflammatory pathways during EVLP provides potential therapeutic targets to improve donor lung quality and enhance clinical outcomes.
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