COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm
Autor
Lee, Wonhwa
Ahn, June Hong
Park, Hee Ho
Kim, Hong Nam
Kim, Hyelim
Yoo, Youngbum
Shin, Hyosoo
Hong, Kyung Soo
Jang, Jong Geol
Park, Chun Gwon
Choi, Eun Young
Bae, Jong-Sup
Seo, Young-Kyo
Institución
Resumen
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.