Tissue factor links inflammation, thrombosis, and senescence in COVID-19.
Tissue factor links inflammation, thrombosis, and senescence in COVID-19.
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DOI：
10.1038/s41598-022-23950-y
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发表时间：
2022-11-18
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
COVID-19 是由 SARS-CoV-2 病毒引起的高度传染性呼吸道感染。受感染的肺上皮细胞会分泌一组趋化因子和细胞因子，引发有害的细胞因子风暴和过度血栓反应。最近的研究提出，病毒诱导的衰老是导致 COVID-19 患者细胞因子释放和炎症的原因。然而，尚不清楚细胞衰老是否通常在病毒感染后引发，以及这些患者中过度激活的炎症和血栓形成如何在功能上相互关联。为了解决这些问题，我们使用从人类患者研究、动物模型以及感染 SARS-CoV-2 和其他呼吸道病毒的细胞系中获得的单细胞和批量 RNA 测序数据集进行了基于生物信息学的荟萃分析。我们发现，大多数 SARS-CoV-2 感染患者的衰老表型显着上调，特别是在受感染的肺上皮细胞中。值得注意的是，组织因子（F3）（外源性凝血途径的关键启动子）的上调与衰老相关分泌表型（SASP）因子的上调同时发生。此外，F3 水平与 COVID-19 患者的衰老和高凝基因特征呈正相关。总之，这些数据证明了呼吸道病毒感染中衰老的普遍性，并表明 F3 是这些疾病状态中炎症、血栓形成和衰老之间的关键联系。
COVID-19 is a highly contagious respiratory infection caused by the SARS-CoV-2 virus. The infected lung epithelial cells secrete a group of chemokines and cytokines, which triggers harmful cytokine storms and hyper-thrombotic responses. Recent studies have proposed that viral-induced senescence is responsible for cytokine release and inflammation in COVID-19 patients. However, it is unknown whether cellular senescence is commonly triggered after viral infection and how inflammation and thrombosis, hyper-activated in these patients, are functionally connected. To address these questions, we conducted a bioinformatics-based meta-analysis using single-cell and bulk RNA sequencing datasets obtained from human patient studies, animal models, and cell lines infected with SARS-CoV-2 and other respiratory viruses. We found that the senescence phenotype is robustly upregulated in most SARS-CoV-2-infected patients, especially in the infected lung epithelial cells. Notably, the upregulation of Tissue factor (F3), a key initiator of the extrinsic blood coagulation pathway, occurs concurrently with the upregulation of the senescence-associated secretory phenotype (SASP) factors. Furthermore, F3 levels are positively correlated with the senescence and hyper-coagulation gene signatures in COVID-19 patients. Together, these data demonstrate the prevalence of senescence in respiratory viral infection and suggest F3 as a critical link between inflammation, thrombosis, and senescence in these disease states.
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影响因子：
12.8
作者：
Hanff TC;Mohareb AM;Giri J;Cohen JB;Chirinos JA
通讯作者：
Chirinos JA
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
46.9
作者：
Chua, Robert Lorenz;Lukassen, Soeren;Eils, Roland
通讯作者：
Eils, Roland
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
32.4
作者：
Hoagland DA;Møller R;Uhl SA;Oishi K;Frere J;Golynker I;Horiuchi S;Panis M;Blanco-Melo D;Sachs D;Arkun K;Lim JK;tenOever BR
通讯作者：
tenOever BR