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A combination of pirfenidone and TGF-β inhibition mitigates cystic echinococcosis-associated hepatic injury

Published online by Cambridge University Press:  15 February 2021

Erqiang Wang Open the ORCID record for Erqiang Wang [Opens in a new window] ,
Zhenyu Liao ,
Lianghai Wang ,
Yuan Liao ,
Xiaodan Xu ,
Ping Liu ,
Xian Wang ,
Jun Hou Open the ORCID record for Jun Hou [Opens in a new window] ,
Huijiao Jiang  and
Xiangwei Wu
...Show all authors
Erqiang Wang
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China Department of Hunan Children's Research Institute, Hunan Children's Hospital, Changsha, China
Zhenyu Liao
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Lianghai Wang
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Yuan Liao
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Xiaodan Xu
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Ping Liu
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Xian Wang
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Jun Hou
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Huijiao Jiang
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Xiangwei Wu*
Affiliation:
Department of Hepatobiliary Surgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
Xueling Chen*
Affiliation:
Department of Basic Medical Sciences, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
*
Author for correspondence: Xueling Chen, E-mail: chenxueling@shzu.edu.cn; Xiangwei Wu, E-mail: wxwshz@126.com
Author for correspondence: Xueling Chen, E-mail: chenxueling@shzu.edu.cn; Xiangwei Wu, E-mail: wxwshz@126.com
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Abstract

Cystic echinococcosis (CE) occurs in the intermediate host's liver, assuming a bladder-like structure surrounded by the host-derived collagen capsule mainly derived from activated hepatic stellate cells (HSCs). However, the effect of CE on liver natural killer (NK) cells and the potential of transforming growth factor-β (TGF-β) signalling inhibition on alleviating CE-related liver damage remain to be explored. Here, by using the CE-mouse model, we revealed that the inhibitory receptors on the surface of liver NK cells were up-regulated, whereas the activating receptors were down-regulated over time. TGF-β1 secretion was elevated in liver tissues and mainly derived from macrophages. A combination of TGF-β signalling inhibitors SB525334 and pirfenidone could reduce the expression of TGF-β1 signalling pathway-related proteins and collagen production. Based on the secretion of TGF-β1, only the pirfenidone group showed a depressing effect. Also, the combination of SB525334 and pirfenidone exhibited a higher potential in effectively alleviating the senescence of the hepatocytes and restoring liver function. Together, TGF-β1 may be a potential target for the treatment of CE-associated liver fibrosis.

Keywords

Cystic echinococcosisEchinococcus granulosushepatocyte senescenceliver fibrosisnatural killer cell
Type
Research Article
Information
Parasitology , Volume 148 , Issue 7 , June 2021 , pp. 767 - 778
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this work.

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