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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Elsevier
2020-11-01
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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. |
first_indexed | 2024-12-24T00:12:32Z |
format | Article |
id | doaj.art-64f9309571754a6682b102a722640965 |
institution | Directory Open Access Journal |
issn | 1347-8613 |
language | English |
last_indexed | 2024-12-24T00:12:32Z |
publishDate | 2020-11-01 |
publisher | Elsevier |
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series | Journal of Pharmacological Sciences |
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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