COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm

Cited 87 time in scopus
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Title
COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm
Author(s)
Wonhwa Lee; J H Ahn; H H Park; H N Kim; H Kim; Youngbum Yoo; Hyosoo Shin; K S Hong; J G Jang; C G Park; E Y Choi; J S Bae; Young Kyo Seo
Bibliographic Citation
Signal Transduction and Targeted Therapy, vol. 5, pp. 186-186
Publication Year
2020
Abstract
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.
ISSN
2095-9907
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41392-020-00292-7
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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