1. Effects of chitinase-3-like protein 1 on brain death-induced hepatocyte apoptosis via PAR2-JNK-caspase-3.
- Author
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Li, Ze-Xin, Yang, Dong-Jing, Huo, Zhong-Kun, Wen, Pei-Hao, Hu, Bo-Wen, Wang, Zhi-Hui, Guo, Wen-Zhi, and Zhang, Shui-Jun
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LIVER cells , *PROTEASE-activated receptors , *APOPTOSIS , *BRAIN death , *CHITIN - Abstract
Hepatocyte apoptosis is a crucial factor affecting liver quality in brain-dead donors. The identification of key molecular proteins involved in brain-death (BD)-induced hepatocyte apoptosis may help determine an effective method for improving the quality of livers from brain-dead donors. In this study, we used in vivo and in vitro models to investigate the role of chitinase-3-like protein 1 (CHI3L1) in promoting liver cell apoptosis after BD. Chitin was used to inhibit CHI3L1 in a rat model of BD. Macrophage polarization of THP-1 cells and hypoxia/reoxygenation (H/R) of LO-2 cells were used to mimic BD-induced cell stress in liver. We found that CHI3L1 played a vital role in promoting liver cell apoptosis. Six hours after BD, CHI3L1 expression was significantly upregulated in liver macrophages and was associated with BD-induced M1 polarization of these cells. In liver cells cultured under H/R conditions, recombinant CHI3L1 activated the protease-activated receptor 2 (PAR2)/c-June N-terminal kinase (JNK) apoptotic pathway and aggravated apoptosis. Compared with the control group, chitin particles inhibited the expression of CHI3L1 in the liver of brain dead rats, thereby reducing activation of the hepatocyte surface receptor, PAR2, and its downstream JNK/caspase-3 signaling pathway, ultimately reducing hepatocyte apoptosis. In conclusion, our results indicate that CHI3L1 relies on a PAR2/JNK-mediated mechanism to promote BD-induced hepatocyte apoptosis. • CHI3L1 upregulated in liver macrophages after Brain death (BD). • CHI3L1 upregulation associated with BD-induced M1 polarization. • CHI3L1 activated PAR2/JNK pathway, promotes BD-induced hepatocyte apoptosis. • Chitin inhibits CHI3L1 expression and PAR2/JNK/caspase-3 signaling pathway. • Chitin reduces hepatocyte apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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