C-reactive protein attenuates CCl4-induced acute liver injury by regulating complement system activation

被引：0

作者：

Tang, Zhao-Ming ^{[1
,2
]}

Yuan, Ping ^{[3
]}

Gao, Ning ^{[4
]}

Lei, Jia-Geng ^{[3
]}

Ahmed, Mustafa ^{[1
,2
]}

Hua, Yu-Xin ^{[3
]}

Yang, Ze-Rui ^{[1
,2
]}

Li, Qiu-Yu ^{[5
]}

Li, Hai-Yun ^{[1
,2
]}

机构：

[1] Xi An Jiao Tong Univ, Sch Basic Med Sci, Xian 710061, Shaanxi, Peoples R China

[2] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Nephrol Nephrol & Crit Care Med, Xian Int Sci & Technol Cooperat Base, Xian 710061, Shaanxi, Peoples R China

[3] Lanzhou Univ, Sch Life Sci, MOE Key Lab Cell Act & Stress Adaptat, Lanzhou 730000, Peoples R China

[4] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Infect Dis, Xian 710061, Shaanxi, Peoples R China

[5] Peking Univ Third Hosp, Dept Resp & Crit Care Med, Beijing 100191, Peoples R China

来源：

MOLECULAR IMMUNOLOGY | 2025年 / 180卷

基金：

中国国家自然科学基金;

关键词：

C -reactive protein; Acute liver injury; Complement system; Inflammation; CARBON-TETRACHLORIDE; INFLAMMATION; MOUSE; CELLS; HEPATOTOXICITY; RELEASE;

D O I：

10.1016/j.molimm.2025.02.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Acute liver injury is liver dysfunction caused by multiple factors without any pre-existing liver disease. C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes, serving as a marker of inflammation and tissue damage. However, its role in CCl4-induced acute liver injury has not been elucidated. Here, we report that CRP protects against CCl4-induced acute liver injury by regulating complement activation. CRP knockout exacerbates CCl4-induced acute liver injury in mice and rats, markedly enhances tissue damage, and reduces survival. Administration of exogenous CRP to CRP-knockout mice rescues the CCl4-induced liver injury phenotype. The protective effect of CRP is independent of its cellular receptor Fc gamma R2b and early metabolic pathways. Instead, CRP suppresses the late-phase amplification of inflammation by inhibiting terminal complement pathway over- activation in injured hepatocytes via factor H recruitment. In complement C3 knockout (C3-/-) mice, the protective effect of CRP against CCl4-induced acute liver injury is lost. These results suggest that CRP can alleviate CCl4-induced acute liver injury by regulating the complement pathway, providing a theoretical basis for CRP's potential involvement and regulation of disease severity.

引用

页码：44 / 54

页数：11

共 53 条

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