Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis

Hepatitis B virus X protein (HBx) and hepatic stellate cells (HSCs) are critical for liver fibrosis development. Anti-fibrosis occurs via reversion to quiescent-type HSCs or clearance of HSCs via apoptosis or ferroptosis. We aimed to elucidate the role of chrysophanol in rat HSC-T6 cells expressing...

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Main Authors: Chan-Yen Kuo, Valeria Chiu, Po-Chun Hsieh, Chun-Yen Huang, S. Joseph Huang, I-Shiang Tzeng, Fu-Ming Tsai, Mao-Liang Chen, Chien-Ting Liu, Yi-Ru Chen
Format: Article
Language:English
Published: Elsevier 2020-11-01
Series:Journal of Pharmacological Sciences
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Online Access:http://www.sciencedirect.com/science/article/pii/S1347861320300797
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author Chan-Yen Kuo
Valeria Chiu
Po-Chun Hsieh
Chun-Yen Huang
S. Joseph Huang
I-Shiang Tzeng
Fu-Ming Tsai
Mao-Liang Chen
Chien-Ting Liu
Yi-Ru Chen
author_facet Chan-Yen Kuo
Valeria Chiu
Po-Chun Hsieh
Chun-Yen Huang
S. Joseph Huang
I-Shiang Tzeng
Fu-Ming Tsai
Mao-Liang Chen
Chien-Ting Liu
Yi-Ru Chen
author_sort Chan-Yen Kuo
collection DOAJ
description Hepatitis B virus X protein (HBx) and hepatic stellate cells (HSCs) are critical for liver fibrosis development. Anti-fibrosis occurs via reversion to quiescent-type HSCs or clearance of HSCs via apoptosis or ferroptosis. We aimed to elucidate the role of chrysophanol in rat HSC-T6 cells expressing HBx and investigate whether chrysophanol (isolated from Rheum palmatum rhizomes) influences cell death via ferroptosis in vitro. Analysis of lipid reactive oxygen species (ROS), Bip, CHOP, p-IRE1α, GPX4, SLC7A11, α-SMA, and CTGF showed that chrysophanol attenuated HBx-repressed cell death. Chrysophanol can impair HBx-induced activation of HSCs via endoplasmic reticulum stress (ER stress) and ferroptosis-dependent and GPX4-independent pathways.
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spelling doaj.art-64f9309571754a6682b102a7226409652022-12-21T17:24:51ZengElsevierJournal of Pharmacological Sciences1347-86132020-11-011443172182Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosisChan-Yen Kuo0Valeria Chiu1Po-Chun Hsieh2Chun-Yen Huang3S. Joseph Huang4I-Shiang Tzeng5Fu-Ming Tsai6Mao-Liang Chen7Chien-Ting Liu8Yi-Ru Chen9Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; Corresponding author.Division of Physical Medicine and Rehabilitation, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanDepartment of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanDepartment of Obstetrics and Gynecology, E-Da Hospital, Kaohsiung, Taiwan; Department of Medical Research, E-Da Hospital, Kaohsiung, TaiwanDepartment of Medical Research, E-Da Hospital, Kaohsiung, Taiwan; School of Medicine, I-Shou University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, University of South Florida, USADepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanDivision of Physical Medicine and Rehabilitation, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanHepatitis B virus X protein (HBx) and hepatic stellate cells (HSCs) are critical for liver fibrosis development. Anti-fibrosis occurs via reversion to quiescent-type HSCs or clearance of HSCs via apoptosis or ferroptosis. We aimed to elucidate the role of chrysophanol in rat HSC-T6 cells expressing HBx and investigate whether chrysophanol (isolated from Rheum palmatum rhizomes) influences cell death via ferroptosis in vitro. Analysis of lipid reactive oxygen species (ROS), Bip, CHOP, p-IRE1α, GPX4, SLC7A11, α-SMA, and CTGF showed that chrysophanol attenuated HBx-repressed cell death. Chrysophanol can impair HBx-induced activation of HSCs via endoplasmic reticulum stress (ER stress) and ferroptosis-dependent and GPX4-independent pathways.http://www.sciencedirect.com/science/article/pii/S1347861320300797Hepatic stellate cellsChrysophanolLipid reactive oxygen speciesER stressFerroptosis
spellingShingle Chan-Yen Kuo
Valeria Chiu
Po-Chun Hsieh
Chun-Yen Huang
S. Joseph Huang
I-Shiang Tzeng
Fu-Ming Tsai
Mao-Liang Chen
Chien-Ting Liu
Yi-Ru Chen
Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis
Journal of Pharmacological Sciences
Hepatic stellate cells
Chrysophanol
Lipid reactive oxygen species
ER stress
Ferroptosis
title Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis
title_full Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis
title_fullStr Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis
title_full_unstemmed Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis
title_short Chrysophanol attenuates hepatitis B virus X protein-induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis
title_sort chrysophanol attenuates hepatitis b virus x protein induced hepatic stellate cell fibrosis by regulating endoplasmic reticulum stress and ferroptosis
topic Hepatic stellate cells
Chrysophanol
Lipid reactive oxygen species
ER stress
Ferroptosis
url http://www.sciencedirect.com/science/article/pii/S1347861320300797
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