한빛사 논문
Wonhwa Lee1, June Hong Ahn2, Hee Ho Park3, Hong Nam Kim4,5, Hyelim Kim6, Youngbum Yoo1, Hyosoo Shin1,6, Kyung Soo Hong7, Jong Geol Jang7, Chun Gwon Park7,8, Eun Young Choi2, Jong-Sup Bae9 and Young-Kyo Seo1
1Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea;
2Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu 42415, Republic of Korea;
3Department of Biotechnology and Bioengineering, Kangwon National University, Chuncheon, Gangwon-do 24341, Republic of Korea;
4Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea;
5Division of Bio-Medical Science and Technology, KIST School, Korea University
of Science and Technology, Seoul 02792, Republic of Korea;
6College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea;
7Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), Suwon, Republic of Korea;
8Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan
University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Republic of Korea and
9College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU MultiOmics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea
Correspondence: Eun Young Choi or Jong-Sup Bae or Young-Kyo Seo
These authors contributed equally: Wonhwa Lee, June Hong Ahn, Hee Ho Park, Hong Nam Kim
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.
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