Cargando…

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

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) ha...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Ji-Xin, Liu, Man, Yu, Guo-Zhi, Zhao, Qian-Qian, Wang, Jian-Ling, Sun, Yan-Hong, Koda, Stephane, Zhang, Beibei, Yu, Qian, Yan, Chao, Tang, Ren-Xian, Jiang, Zhi-Hua, Zheng, Kui-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627039/
https://www.ncbi.nlm.nih.gov/pubmed/36339341
http://dx.doi.org/10.3389/fcimb.2022.1011378
_version_ 1784822875118632960
author Liu, Ji-Xin
Liu, Man
Yu, Guo-Zhi
Zhao, Qian-Qian
Wang, Jian-Ling
Sun, Yan-Hong
Koda, Stephane
Zhang, Beibei
Yu, Qian
Yan, Chao
Tang, Ren-Xian
Jiang, Zhi-Hua
Zheng, Kui-Yang
author_facet Liu, Ji-Xin
Liu, Man
Yu, Guo-Zhi
Zhao, Qian-Qian
Wang, Jian-Ling
Sun, Yan-Hong
Koda, Stephane
Zhang, Beibei
Yu, Qian
Yan, Chao
Tang, Ren-Xian
Jiang, Zhi-Hua
Zheng, Kui-Yang
author_sort Liu, Ji-Xin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9627039
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96270392022-11-03 Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2 Liu, Ji-Xin Liu, Man Yu, Guo-Zhi Zhao, Qian-Qian Wang, Jian-Ling Sun, Yan-Hong Koda, Stephane Zhang, Beibei Yu, Qian Yan, Chao Tang, Ren-Xian Jiang, Zhi-Hua Zheng, Kui-Yang Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2022-10-19 /pmc/articles/PMC9627039/ /pubmed/36339341 http://dx.doi.org/10.3389/fcimb.2022.1011378 Text en Copyright © 2022 Liu, Liu, Yu, Zhao, Wang, Sun, Koda, Zhang, Yu, Yan, Tang, Jiang and Zheng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Liu, Ji-Xin
Liu, Man
Yu, Guo-Zhi
Zhao, Qian-Qian
Wang, Jian-Ling
Sun, Yan-Hong
Koda, Stephane
Zhang, Beibei
Yu, Qian
Yan, Chao
Tang, Ren-Xian
Jiang, Zhi-Hua
Zheng, Kui-Yang
Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2
title Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2
title_full Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2
title_fullStr Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2
title_full_unstemmed Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2
title_short Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2
title_sort clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627039/
https://www.ncbi.nlm.nih.gov/pubmed/36339341
http://dx.doi.org/10.3389/fcimb.2022.1011378
work_keys_str_mv AT liujixin clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT liuman clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT yuguozhi clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT zhaoqianqian clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT wangjianling clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT sunyanhong clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT kodastephane clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT zhangbeibei clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT yuqian clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT yanchao clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT tangrenxian clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT jiangzhihua clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2
AT zhengkuiyang clonorchissinensisinfectioninduceshepatobiliaryinjuryviadisturbingsphingolipidmetabolismandactivatingsphingosine1phosphatereceptor2