Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice

Cong,Min; Zhao,Weihua; Liu,Tianhui; Wang,Ping; Fan,Xu; Zhai,Qingling; Bao,Xiaoli; Zhang,Dong; You,Hong; Kisseleva,Tatiana; Brenner,David A.; Jia,Jidong; Zhuang,Hui

doi:10.3892/ijmm.2017.3028

Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice

Authors:
- Min Cong
- Weihua Zhao
- Tianhui Liu
- Ping Wang
- Xu Fan
- Qingling Zhai
- Xiaoli Bao
- Dong Zhang
- Hong You
- Tatiana Kisseleva
- David A. Brenner
- Jidong Jia
- Hui Zhuang
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Affiliations: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P.R. China, Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases, Beijing 100050, P.R. China, Department of Surgery, UC San Diego, San Diego, La Jolla, CA 92093, USA, Department of Medicine, UC San Diego, San Diego, La Jolla, CA 92093, USA
Published online on: June 14, 2017 https://doi.org/10.3892/ijmm.2017.3028
Pages: 454-464
Copyright: © Cong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28-30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-β1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation.

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