Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2.

Publisher: Frontiers Media SA Country of Publication: Switzerland NLM ID: 101585359 Publication Model: eCollection Cited Medium: Internet ISSN: 2235-2988 (Electronic) Linking ISSN: 22352988 NLM ISO Abbreviation: Front Cell Infect Microbiol Subsets: MEDLINE

Original Publication: Lausanne : Frontiers Media SA

Clonorchiasis*/metabolism ; Clonorchiasis*/pathology ; Clonorchis sinensis* ; Bile Duct Neoplasms*/metabolism ; Bile Duct Neoplasms*/pathology; Mice ; Animals ; Sphingosine-1-Phosphate Receptors ; Bile Ducts, Intrahepatic/metabolism ; Bile Ducts, Intrahepatic/pathology ; Inflammation/pathology ; Fibrosis ; Sphingolipids

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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Liu, Liu, Yu, Zhao, Wang, Sun, Koda, Zhang, Yu, Yan, Tang, Jiang and Zheng.)

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Keywords: Clonorchis sinensis; biliary epithelial cells (BECs); hepatobiliary injuries; sphingolipid metabolism; sphingosine 1-phosphate receptor 2

0 (Sphingosine-1-Phosphate Receptors)
26993-30-6 (sphingosine 1-phosphate)
0 (Sphingolipids)

Date Created: 20221107 Date Completed: 20221108 Latest Revision: 20221222

20250114

PMC9627039

10.3389/fcimb.2022.1011378

36339341