COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm
In: Signal Transduction and Targeted Therapy Signal Transduction and Targeted Therapy, Jg. 5 (2020), Heft 1, S. 1-11
Online
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Zugriff:
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-κB 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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COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm
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Autor/in / Beteiligte Person: | Chun Gwon Park ; Seo, Young-Kyo ; Hee Ho Park ; Jong Geol Jang ; Hong Nam Kim ; June Hong Ahn ; Kyung Soo Hong ; Bae, Jong-Sup ; Eun Young Choi ; Shin, Hyosoo ; Kim, Hyelim ; Yoo, Youngbum ; Lee, Wonhwa |
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Zeitschrift: | Signal Transduction and Targeted Therapy Signal Transduction and Targeted Therapy, Jg. 5 (2020), Heft 1, S. 1-11 |
Veröffentlichung: | Springer Science and Business Media LLC, 2020 |
Medientyp: | unknown |
ISSN: | 2059-3635 (print) |
DOI: | 10.1038/s41392-020-00292-7 |
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