Effects of chitinase-3-like protein 1 on brain death-induced hepatocyte apoptosis via PAR2-JNK-caspase-3
Autor: | Bo-Wen Hu, Wang Zhihui, Wen Peihao, Shuijun Zhang, Wenzhi Guo, Dongjing Yang, Zhong-Kun Huo, Zexin Li |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Brain Death THP-1 Cells Biophysics Macrophage polarization Caspase 3 Apoptosis Chitin Biochemistry Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Animals Humans Receptor PAR-2 Chitinase-3-Like Protein 1 Receptor Molecular Biology Cells Cultured Chemistry Kinase Liver cell JNK Mitogen-Activated Protein Kinases Cell Biology Cell biology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Hepatocyte Hepatocytes RNA Interference Signal transduction Signal Transduction |
Zdroj: | Biochemical and biophysical research communications. 552 |
ISSN: | 1090-2104 |
Popis: | 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. |
Databáze: | OpenAIRE |
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