Chitinase 3-like-1 is a therapeutic target that mediates the effects of aging in COVID-19

被引：31

作者：

Kamle, Suchitra ^{[1
]}

Ma, Bing ^{[1
]}

He, Chuan Hua ^{[1
]}

Akosman, Bedia ^{[1
]}

Zhou, Yang ^{[1
]}

Lee, Chang-Min ^{[1
]}

El-Deiry, Wafik S. ^{[2
,3
,4
,5
]}

Huntington, Kelsey ^{[2
,3
,4
,5
]}

Liang, Olin ^{[3
,4
,5
]}

Machan, Jason T. ^{[6
]}

Kang, Min-Jong ^{[7
]}

Shin, Hyeon Jun ^{[7
]}

Mizoguchi, Emiko ^{[1
,8
]}

Lee, Chun Geun ^{[1
]}

Elias, Jack A. ^{[1
,4
,5
,9
]}

机构：

[1] Brown Univ, Mol Microbiol & Immunol, Providence, RI 02912 USA

[2] Brown Univ, Pathol & Lab Med, Providence, RI 02912 USA

[3] Brown Univ, Hematol Oncol Div, Dept Med, Providence, RI 02912 USA

[4] Brown Univ, Joint Program Canc Biol, Providence, RI 02912 USA

[5] Brown Univ, Canc Ctr, Providence, RI 02912 USA

[6] Brown Univ, Warren Alpert Med Sch, Dept Biostat, Lifespan Hlth Syst, Providence, RI 02912 USA

[7] Yale Univ, Sch Med, Dept Internal Med, Sect Pulm Crit Care & Sleep Med, New Haven, CT 06510 USA

[8] Kurume Univ, Sch Med, Dept Immunol, Kurume, Fukuoka, Japan

[9] Brown Univ, Dept Med, Providence, RI 02912 USA

来源：

JCI INSIGHT | 2021年 / 6卷 / 21期

关键词：

BREAST REGRESSION PROTEIN-39; CORONAVIRUS DISEASE 2019; SERUM YKL-40 LEVEL; CLINICAL CHARACTERISTICS; TISSUE RESPONSES; LUNG; INFLAMMATION; ASTHMA; CHI3L1; CONTRIBUTES;

D O I：

10.1172/jci.insight.148749

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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

引用

页数：19

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