期刊
JCI INSIGHT
卷 6, 期 21, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.148749
关键词
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资金
- NIH from National Heart, Lung, and Blood Institute [01 HL108638, P01 HL114501, R01 HL115813]
- National Institute of Aging [R01 AG053495]
- Department of Defense [W81XWH-17-1-0196]
- Brown University
- NIH [P20 GM119943]
CHI3L1 is induced in elderly individuals and patients with comorbid diseases, playing a significant role in stimulating ACE2 and SPP during SC2 infection, and its levels correlate with COVID-19 severity.
COVID-19 is caused by SARS-CoV-2 (SC2) and is more prevalent and severe in elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here, we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor angiotensin converting enzyme 2 (ACE2) and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging, and that anti-CHI3L1, kasugamycin, and inhibitors of phosphorylation abrogate these ACE2- and SPP-inductive events. Human studies also demonstrate that the levels of circulating CHI3L1 are increased in the elderly and patients with CM, where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP, that this induction is a major mechanism contributing to the effects of aging during SC2 infection, and that CHI3L1 co-opts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive
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