COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm.
Signal Transduct Target Ther
; 5(1): 186, 2020 09 03.
Article
in En
| MEDLINE
| ID: mdl-32883951
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Leukocytes, Mononuclear
/
Cholesterol
/
Coronavirus Infections
/
Sterol Regulatory Element Binding Protein 2
/
Host-Pathogen Interactions
/
Betacoronavirus
/
Cytokine Release Syndrome
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Language:
En
Journal:
Signal Transduct Target Ther
Year:
2020
Document type:
Article