Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads Pathway
Liver fibrosis is an important stage in the progression of liver injury into cirrhosis or even liver cancer. Hepatic stellate cells (HSCs) are induced by transforming growth factor-β1 (TGF-β1) to produce α-smooth muscle actin (α-SMA) and collagens in liver fibrosis. Butaselen (BS), which was previou...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-09-01
|
Series: | Frontiers in Molecular Biosciences |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.690170/full |
id |
doaj-6efe36b03007483cbb4015368a658121 |
---|---|
record_format |
Article |
spelling |
doaj-6efe36b03007483cbb4015368a6581212021-09-03T23:38:07ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-09-01810.3389/fmolb.2021.690170690170Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads PathwayWenxuan Jiao0Man Bai1Man Bai2Hanwei Yin3Jiayi Liu4Jing Sun5Xiaoxia Su6Huihui Zeng7Jinhua Wen8State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaDepartment of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaShanghai Yuanxi Medicine Corp, Shanghai, ChinaDepartment of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaDepartment of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaDepartment of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaLiver fibrosis is an important stage in the progression of liver injury into cirrhosis or even liver cancer. Hepatic stellate cells (HSCs) are induced by transforming growth factor-β1 (TGF-β1) to produce α-smooth muscle actin (α-SMA) and collagens in liver fibrosis. Butaselen (BS), which was previously synthesized by our group, is an organic selenium compound that exerts antioxidant and tumor cell apoptosis–promoting effects by inhibiting the thioredoxin (Trx)/thioredoxin reductase (TrxR) system. The aim of this study was to investigate the potential effects of BS on liver fibrosis and explore the underlying molecular mechanisms of its action. Liver fibrosis models were established using male BALB/c mice through intraperitoneal injection of CCl4. BS was administered orally once daily at a dose of 36, 90, or 180 mg/kg. Silymarin (Si), which is a drug used for patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, was administered at a dose of 30 mg/kg per day as a control. The action mechanisms of BS against liver fibrosis progression were examined in HSCs. The study revealed that the activity and expression levels of TrxR were elevated in the mouse liver and serum after CCl4-induced liver fibrosis. Oral administration of BS relieved the pathological state of mice with liver fibrosis, showing significant therapeutic effects against liver fibrosis. Moreover, BS not only induced HSC apoptosis but also inhibited the production of α-SMA and collagens by HSCs by downregulating the TGF-β1 expression and blocking the TGF-β1/Smads pathway. The results of the study indicated that BS inhibited liver fibrosis by regulating the TGF-β1/Smads pathway.https://www.frontiersin.org/articles/10.3389/fmolb.2021.690170/fullliver fibrosishepatic stellate cellsthioredoxin reductasetransforming growth factor-β1collagenα-SMA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wenxuan Jiao Man Bai Man Bai Hanwei Yin Jiayi Liu Jing Sun Xiaoxia Su Huihui Zeng Jinhua Wen |
spellingShingle |
Wenxuan Jiao Man Bai Man Bai Hanwei Yin Jiayi Liu Jing Sun Xiaoxia Su Huihui Zeng Jinhua Wen Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads Pathway Frontiers in Molecular Biosciences liver fibrosis hepatic stellate cells thioredoxin reductase transforming growth factor-β1 collagen α-SMA |
author_facet |
Wenxuan Jiao Man Bai Man Bai Hanwei Yin Jiayi Liu Jing Sun Xiaoxia Su Huihui Zeng Jinhua Wen |
author_sort |
Wenxuan Jiao |
title |
Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads Pathway |
title_short |
Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads Pathway |
title_full |
Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads Pathway |
title_fullStr |
Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads Pathway |
title_full_unstemmed |
Therapeutic Effects of an Inhibitor of Thioredoxin Reductase on Liver Fibrosis by Inhibiting the Transforming Growth Factor-β1/Smads Pathway |
title_sort |
therapeutic effects of an inhibitor of thioredoxin reductase on liver fibrosis by inhibiting the transforming growth factor-β1/smads pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Biosciences |
issn |
2296-889X |
publishDate |
2021-09-01 |
description |
Liver fibrosis is an important stage in the progression of liver injury into cirrhosis or even liver cancer. Hepatic stellate cells (HSCs) are induced by transforming growth factor-β1 (TGF-β1) to produce α-smooth muscle actin (α-SMA) and collagens in liver fibrosis. Butaselen (BS), which was previously synthesized by our group, is an organic selenium compound that exerts antioxidant and tumor cell apoptosis–promoting effects by inhibiting the thioredoxin (Trx)/thioredoxin reductase (TrxR) system. The aim of this study was to investigate the potential effects of BS on liver fibrosis and explore the underlying molecular mechanisms of its action. Liver fibrosis models were established using male BALB/c mice through intraperitoneal injection of CCl4. BS was administered orally once daily at a dose of 36, 90, or 180 mg/kg. Silymarin (Si), which is a drug used for patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, was administered at a dose of 30 mg/kg per day as a control. The action mechanisms of BS against liver fibrosis progression were examined in HSCs. The study revealed that the activity and expression levels of TrxR were elevated in the mouse liver and serum after CCl4-induced liver fibrosis. Oral administration of BS relieved the pathological state of mice with liver fibrosis, showing significant therapeutic effects against liver fibrosis. Moreover, BS not only induced HSC apoptosis but also inhibited the production of α-SMA and collagens by HSCs by downregulating the TGF-β1 expression and blocking the TGF-β1/Smads pathway. The results of the study indicated that BS inhibited liver fibrosis by regulating the TGF-β1/Smads pathway. |
topic |
liver fibrosis hepatic stellate cells thioredoxin reductase transforming growth factor-β1 collagen α-SMA |
url |
https://www.frontiersin.org/articles/10.3389/fmolb.2021.690170/full |
work_keys_str_mv |
AT wenxuanjiao therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway AT manbai therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway AT manbai therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway AT hanweiyin therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway AT jiayiliu therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway AT jingsun therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway AT xiaoxiasu therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway AT huihuizeng therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway AT jinhuawen therapeuticeffectsofaninhibitorofthioredoxinreductaseonliverfibrosisbyinhibitingthetransforminggrowthfactorb1smadspathway |
_version_ |
1717815676059516928 |