Chitinase 3-like-1 is a therapeutic target that mediates the effects of aging in COVID-19.
COVID-19
Immunotherapy
Molecular pathology
Therapeutics
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
08 11 2021
08 11 2021
Historique:
received:
15
02
2021
accepted:
29
09
2021
entrez:
8
11
2021
pubmed:
9
11
2021
medline:
16
11
2021
Statut:
epublish
Résumé
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 therapeutic target in COVID-19.
Identifiants
pubmed: 34747367
pii: 148749
doi: 10.1172/jci.insight.148749
pmc: PMC8663553
doi:
pii:
Substances chimiques
Aminoglycosides
0
CHI3L1 protein, human
0
Chil1 protein, mouse
0
Chitinase-3-Like Protein 1
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
kasugamycin
O957UYB9DY
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM119943
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL115813
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG053495
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL114501
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL108638
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG053495
Pays : United States
Commentaires et corrections
Type : UpdateOf
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