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  • COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm #MMPMID32883951
  • Lee W; Ahn JH; Park HH; Kim HN; Kim H; Yoo Y; Shin H; Hong KS; Jang JG; Park CG; Choi EY; Bae JS; Seo YK
  • Signal Transduct Target Ther 2020[Sep]; 5 (1): 186 PMID32883951show ga
  • 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-kappaB 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.
  • |Betacoronavirus/immunology/*pathogenicity[MESH]
  • |COVID-19[MESH]
  • |Case-Control Studies[MESH]
  • |Cholesterol/*biosynthesis[MESH]
  • |Coronavirus Infections/*genetics/immunology/mortality/virology[MESH]
  • |Cytokine Release Syndrome/*genetics/immunology/mortality/virology[MESH]
  • |Gene Expression Regulation[MESH]
  • |Heat-Shock Proteins/genetics/immunology[MESH]
  • |Host-Pathogen Interactions/*genetics/immunology[MESH]
  • |Humans[MESH]
  • |Intensive Care Units[MESH]
  • |Interleukin-1beta/genetics/immunology[MESH]
  • |L-Lactate Dehydrogenase/genetics/immunology[MESH]
  • |Leukocytes, Mononuclear/*immunology/metabolism/virology[MESH]
  • |Lung/immunology/metabolism/virology[MESH]
  • |NF-kappa B/genetics/immunology[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*genetics/immunology/mortality/virology[MESH]
  • |Primary Cell Culture[MESH]
  • |Proprotein Convertase 9/genetics/immunology[MESH]
  • |SARS-CoV-2[MESH]
  • |Signal Transduction[MESH]
  • |Sterol Regulatory Element Binding Protein 2/*genetics/immunology[MESH]
  • |Survival Analysis[MESH]
  • |Tumor Necrosis Factor-alpha/genetics/immunology[MESH]

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  • suck abstract from ncbi

    186 1.5 2020