Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes

Abstract Hepatitis C virus (HCV) infection of hepatocytes promotes liver fibrosis by activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix in liver tissue. Whether or not host factors released from the HCV-infected hepatocytes play role in HSCs activation is un...

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Autores principales:	Ju-Chien Cheng, Ching-Ping Tseng, Mei-Huei Liao, Cheng-Yuan Peng, Jau-Song Yu, Po-Heng Chuang, Jing-Tang Huang, Jeremy J. W. Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e46f0db66ae743b08ca8c05f3e859002
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spelling	oai:doaj.org-article:e46f0db66ae743b08ca8c05f3e8590022021-12-02T15:05:45ZActivation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes10.1038/s41598-017-04259-72045-2322https://doaj.org/article/e46f0db66ae743b08ca8c05f3e8590022017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04259-7https://doaj.org/toc/2045-2322Abstract Hepatitis C virus (HCV) infection of hepatocytes promotes liver fibrosis by activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix in liver tissue. Whether or not host factors released from the HCV-infected hepatocytes play role in HSCs activation is unclear. In this study, HSCs were activated by the conditioned medium derived from HCV replicon cells. Secretomic profiling of HCV replicon cells and the parental Huh7 cells revealed ubiquitin carboxy-terminal hydrolase L1 (UCHL1) as a novel secreted protein from HCV-infected hepatocytes. UCHL1 expression in hepatocytes was induced by HCV infection. UCHL1 was expressed in the liver and found in the plasma of patients with chronic hepatitis C. Molecular analysis by use of the anti-UCHL1 neutralization antibody and purified UCHL1 protein showed that secreted UCHL1 protein was bound to the cell surface of HSCs and activated JNK signaling leading to overexpression of alpha-smooth muscle actin and the activation of HSCs. These results provide further for understanding the underlying mechanism in HCV-mediated hepatic fibrogenesis.Ju-Chien ChengChing-Ping TsengMei-Huei LiaoCheng-Yuan PengJau-Song YuPo-Heng ChuangJing-Tang HuangJeremy J. W. ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ju-Chien Cheng Ching-Ping Tseng Mei-Huei Liao Cheng-Yuan Peng Jau-Song Yu Po-Heng Chuang Jing-Tang Huang Jeremy J. W. Chen Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes
description	Abstract Hepatitis C virus (HCV) infection of hepatocytes promotes liver fibrosis by activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix in liver tissue. Whether or not host factors released from the HCV-infected hepatocytes play role in HSCs activation is unclear. In this study, HSCs were activated by the conditioned medium derived from HCV replicon cells. Secretomic profiling of HCV replicon cells and the parental Huh7 cells revealed ubiquitin carboxy-terminal hydrolase L1 (UCHL1) as a novel secreted protein from HCV-infected hepatocytes. UCHL1 expression in hepatocytes was induced by HCV infection. UCHL1 was expressed in the liver and found in the plasma of patients with chronic hepatitis C. Molecular analysis by use of the anti-UCHL1 neutralization antibody and purified UCHL1 protein showed that secreted UCHL1 protein was bound to the cell surface of HSCs and activated JNK signaling leading to overexpression of alpha-smooth muscle actin and the activation of HSCs. These results provide further for understanding the underlying mechanism in HCV-mediated hepatic fibrogenesis.
format	article
author	Ju-Chien Cheng Ching-Ping Tseng Mei-Huei Liao Cheng-Yuan Peng Jau-Song Yu Po-Heng Chuang Jing-Tang Huang Jeremy J. W. Chen
author_facet	Ju-Chien Cheng Ching-Ping Tseng Mei-Huei Liao Cheng-Yuan Peng Jau-Song Yu Po-Heng Chuang Jing-Tang Huang Jeremy J. W. Chen
author_sort	Ju-Chien Cheng
title	Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes
title_short	Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes
title_full	Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes
title_fullStr	Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes
title_full_unstemmed	Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes
title_sort	activation of hepatic stellate cells by the ubiquitin c-terminal hydrolase 1 protein secreted from hepatitis c virus-infected hepatocytes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e46f0db66ae743b08ca8c05f3e859002
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Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes

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