Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2022.1011378
Keywords
Clonorchis sinensis; hepatobiliary injuries; biliary epithelial cells (BECs); sphingolipid metabolism; sphingosine 1-phosphate receptor 2
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Funding
- National Natural Science Foundation of China [82172297]
- Xuzhou Medical University [D2019040]
- Priority Academic Program Development of Jiangsu Higher Education Institutions of China
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This study revealed that C. sinensis infection alters bioactive lipids and sphingolipid metabolic pathways in mice liver. Additionally, S1PR2 plays a predominant role in biliary epithelial cells affected by C. sinensis infection. The specific antagonist of S1PR2, JTE-013, effectively inhibits hepatobiliary pathological injuries caused by C. sinensis infection.
Clonorchis sinensis (C. sinensis) infection induces severe hepatobiliary injuries, which can cause inflammation, periductal fibrosis, and even cholangiocarcinoma. Sphingolipid metabolic pathways responsible for the generation of sphingosine-1-phosphate (S1P) and its receptor S1P receptors (S1PRs) have been implicated in many liver-related diseases. However, the role of S1PRs in C. sinensis-mediated biliary epithelial cells (BECs) proliferation and hepatobiliary injury has not been elucidated. In the present study, we found that C. sinensis infection resulted in alteration of bioactive lipids and sphingolipid metabolic pathways in mice liver. Furthermore, S1PR2 was predominantly activated among these S1PRs in BECs both in vivo and in vitro. Using JTE-013, a specific antagonist of S1PR2, we found that the hepatobiliary pathological injuries, inflammation, bile duct hyperplasia, and periductal fibrosis can be significantly inhibited in C. sinensis-infected mice. In addition, both C. sinensis excretory-secretory products (CsESPs)- and S1P-induced activation of AKT and ERK1/2 were inhibited by JTE-013 in BECs. Therefore, the sphingolipid metabolism pathway and S1PR2 play an important role, and may serve as potential therapeutic targets in hepatobiliary injury caused by C. sinensis-infection.
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