期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 5, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41392-020-00292-7
关键词
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资金
- National Research Foundation of Korea (NRF) - KRIBB Research Initiative Program [OGM4391913, KGM5391911]
- National Research Foundation of Korea (NRF) - Korean Government (MSIT) [2018R1A2A3075013, 2019R1C1C1006300, 2019R1A4A1028700, 2020R1A4A4079817, 2020R1A2C1004131]
- Ministry of Education [NRF-2018R1D1A1B07050422]
- KIST Institutional Program [2V07950]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI15C0001]
- National Research Council of Science & Technology (NST), Republic of Korea [KGM5391911] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2V07830, 2019R1A4A1028700, 2019R1C1C1006300, 2020R1A4A4079817] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients' blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-kappa B suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.
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