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Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway

Liver fibrosis is a serious disease that is characterized by the excess deposition of extracellular matrix (ECM) components. Activated hepatic stellate cells (HSCs) are a major source of ECM and serve as a key regulator in liver fibrogenesis. Inactivation of HSCs is essential for liver fibrotic regr...

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Autores principales: Chen, Jinling, Xu, Tianhua, Zhu, Dandan, Wang, Jianxin, Huang, Caiqun, Lyu, Lei, Hu, Bin, Sun, Wei, Duan, Yinong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973363/
https://www.ncbi.nlm.nih.gov/pubmed/27468691
http://dx.doi.org/10.1038/cddis.2016.228
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author Chen, Jinling
Xu, Tianhua
Zhu, Dandan
Wang, Jianxin
Huang, Caiqun
Lyu, Lei
Hu, Bin
Sun, Wei
Duan, Yinong
author_facet Chen, Jinling
Xu, Tianhua
Zhu, Dandan
Wang, Jianxin
Huang, Caiqun
Lyu, Lei
Hu, Bin
Sun, Wei
Duan, Yinong
author_sort Chen, Jinling
collection PubMed
description Liver fibrosis is a serious disease that is characterized by the excess deposition of extracellular matrix (ECM) components. Activated hepatic stellate cells (HSCs) are a major source of ECM and serve as a key regulator in liver fibrogenesis. Inactivation of HSCs is essential for liver fibrotic regression. The present study explores the underlying mechanisms of Schistosoma japonicum egg antigen p40 (Sjp40) promoting senescence in HSCs and antifibrosis. For the first time we report that Sjp40 inhibits the activation and proliferation of an immortalized human HSC line (LX-2 cells) and promotes cellular senescence and cell cycle arrest. Sjp40 through action on the STAT3/p53/p21 pathway triggered cellular senescence, while knockdown of p53 or STAT3 partly restored cell senescence. In addition, Sjp40-induced cellular senescence caused LX-2 cells to be more sensitive to a human NK cell line (YT cells). Together these findings provide novel insights into the mechanism of antifibrosis and may have implications for the development of antifibrosis therapies.
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spelling pubmed-49733632016-08-29 Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway Chen, Jinling Xu, Tianhua Zhu, Dandan Wang, Jianxin Huang, Caiqun Lyu, Lei Hu, Bin Sun, Wei Duan, Yinong Cell Death Dis Original Article Liver fibrosis is a serious disease that is characterized by the excess deposition of extracellular matrix (ECM) components. Activated hepatic stellate cells (HSCs) are a major source of ECM and serve as a key regulator in liver fibrogenesis. Inactivation of HSCs is essential for liver fibrotic regression. The present study explores the underlying mechanisms of Schistosoma japonicum egg antigen p40 (Sjp40) promoting senescence in HSCs and antifibrosis. For the first time we report that Sjp40 inhibits the activation and proliferation of an immortalized human HSC line (LX-2 cells) and promotes cellular senescence and cell cycle arrest. Sjp40 through action on the STAT3/p53/p21 pathway triggered cellular senescence, while knockdown of p53 or STAT3 partly restored cell senescence. In addition, Sjp40-induced cellular senescence caused LX-2 cells to be more sensitive to a human NK cell line (YT cells). Together these findings provide novel insights into the mechanism of antifibrosis and may have implications for the development of antifibrosis therapies. Nature Publishing Group 2016-07 2016-07-28 /pmc/articles/PMC4973363/ /pubmed/27468691 http://dx.doi.org/10.1038/cddis.2016.228 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Chen, Jinling
Xu, Tianhua
Zhu, Dandan
Wang, Jianxin
Huang, Caiqun
Lyu, Lei
Hu, Bin
Sun, Wei
Duan, Yinong
Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway
title Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway
title_full Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway
title_fullStr Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway
title_full_unstemmed Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway
title_short Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway
title_sort egg antigen p40 of schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the stat3/p53/p21 pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973363/
https://www.ncbi.nlm.nih.gov/pubmed/27468691
http://dx.doi.org/10.1038/cddis.2016.228
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