HMGB1 as a potential biomarker and therapeutic target for severe COVID-19.
HMGB1 as a potential biomarker and therapeutic target for severe COVID-19.
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DOI：
10.1016/j.heliyon.2020.e05672
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发表时间：
2020-12
期刊：
影响因子：
4
通讯作者：
Tang D
中科院分区：
文献类型：
--
作者：
Chen R;Huang Y;Quan J;Liu J;Wang H;Billiar TR;Lotze MT;Zeh HJ;Kang R;Tang D
COVID-19因其在全球迅速传播，发病率和相关死亡率高而引起全球关注。严重的COVID-19可并发急性呼吸窘迫综合征、脓毒症和脓毒性休克，导致死亡。这些并发症被认为是由于免疫系统的过度激活，导致与多器官衰竭相关的细胞因子风暴综合征。在这里，我们报告了高迁移率族蛋白1（HMGB 1），一种典型的损伤相关分子模式（DAMP）和致命炎症的中心介质，可能是COVID-19创新治疗策略的潜在靶点。重症COVID-19患者血清HMGB 1升高（189.40 ± 140.88 ng/ml）。外源性HMGB 1诱导肺泡上皮细胞表达SARS-CoV-2进入受体ACE 2重要的是，HMGB 1-AGER通路的遗传（使用AGER siRNA）或药理学（使用曲马多菌素、氯喹、羟氯喹和FPS-ZM 1）抑制可阻断ACE 2表达。因此，HMGB 1抑制剂同样是治疗COVID-19患者的有前景的候选药物。HMGB 1; COVID-19;细胞培养;细胞死亡;炎症;传染病;免疫学;微生物学;病毒学
COVID-19 has attracted global attention due to its rapid spread around the world with substantial morbidity and associated mortality. Severe COVID-19 can be complicated by the acute respiratory distress syndrome, sepsis and septic shock leading to death. These complications are thought to result from an overactivation of the immune system, leading to a cytokine storm syndrome associated with multiple organ failure. Here, we report that high mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) and a central mediator of lethal inflammation, could be a potential target for innovative therapeutic strategies for COVID-19. Serum HMGB1 in severe COVID-19 patients is elevated (189.40 ± 140.88 ng/ml). Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner. Importantly, genetic (using AGER siRNA) or pharmacological (using glycyrrhizin, chloroquine, hydroxychloroquine, and FPS-ZM1) inhibition of the HMGB1-AGER pathway blocks ACE2 expression. Thus, HMGB1 inhibitors are likewise promising drug candidates for the treatment of patients suffering from COVID-19. HMGB1; COVID-19; Cell culture; Cell death; Inflammation; Infectious disease; Immunology; Microbiology; Virology
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影响因子：
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作者：
Mollica, Luca;De Marchis, Francesco;Bianchi, Marco E.
通讯作者：
Bianchi, Marco E.
影响因子：
10.6
作者：
Kang, Rui;Chen, Ruochan;Zhang, Qiuhong;Hou, Wen;Wu, Sha;Cao, Lizhi;Huang, Jin;Yu, Yan;Fan, Xue-gong;Yan, Zhengwen;Sun, Xiaofang;Wang, Haichao;Wang, Qingde;Tsung, Allan;Billiar, Timothy R.;Zeh, Herbert J., III;Lotze, Michael T.;Tang, Daolin
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Tang, Daolin
影响因子：
5.8
作者：
Oczypok EA;Perkins TN;Oury TD
通讯作者：
Oury TD
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影响因子：
5.8
作者：
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通讯作者：
Sama AE
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影响因子：
13.3
作者：
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通讯作者：
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