Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide
While transforming growth factor-β (TGF-β) is known to be a key inducer of hepatic stellate cell (HSC) activation during liver fibrosis but it is unclear which TGF-β receptor is required for this HSC-mediated fibrogenesis. Here, we report that abrogation of TGF-β type I receptor ALK5 in HSC activa...
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doaj-7c6dea60ed4b40f09df0186cc8ce33062020-11-24T21:35:04ZengPrince of Songkla UniversitySongklanakarin Journal of Science and Technology (SJST)0125-33952018-04-0140231432010.14456/sjst-psu.2018.31Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamideSomyoth Sridurongrit0Chen Ke1Wanthita Kongphat2Arnon Pudgerd3Chanyatip Suwannasing4Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400 ThailandDepartment of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400 ThailandGraduate Program of Toxicology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400 ThailandDepartment of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400 ThailandDepartment of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400 ThailandWhile transforming growth factor-β (TGF-β) is known to be a key inducer of hepatic stellate cell (HSC) activation during liver fibrosis but it is unclear which TGF-β receptor is required for this HSC-mediated fibrogenesis. Here, we report that abrogation of TGF-β type I receptor ALK5 in HSC activation led to reduced collagen deposition and a decreased number of myofibroblasts in livers of mutant mice lacking ALK5 in HSC (Alk5/GFAP-Cre mice) following thioacetamide (TAA) exposure. The reduced fibrosis was accompanied by decreased expression of HSC activation markers in livers. In addition, Alk5/GFAP-Cre mice exhibited decreased immune cell infiltration and reduced production of inflammatory cytokines. Associated with reduced fibrosis and inflammation, amelioration of liver injury was observed in Alk5/GFAP-Cre mice after TAA treatment. In conclusion, our results indicated that TGF-β signaling via ALK5 in HSC enhanced liver fibrogenesis and inflammation led to amplification of hepatic injury in mice exposed to TAA.http://rdo.psu.ac.th/sjstweb/journal/40-2/40-2-7.pdfTGF-βALK5hepatic stellate cellsfibrosisliver injury |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Somyoth Sridurongrit Chen Ke Wanthita Kongphat Arnon Pudgerd Chanyatip Suwannasing |
spellingShingle |
Somyoth Sridurongrit Chen Ke Wanthita Kongphat Arnon Pudgerd Chanyatip Suwannasing Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide Songklanakarin Journal of Science and Technology (SJST) TGF-β ALK5 hepatic stellate cells fibrosis liver injury |
author_facet |
Somyoth Sridurongrit Chen Ke Wanthita Kongphat Arnon Pudgerd Chanyatip Suwannasing |
author_sort |
Somyoth Sridurongrit |
title |
Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide |
title_short |
Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide |
title_full |
Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide |
title_fullStr |
Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide |
title_full_unstemmed |
Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide |
title_sort |
abrogation of alk5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide |
publisher |
Prince of Songkla University |
series |
Songklanakarin Journal of Science and Technology (SJST) |
issn |
0125-3395 |
publishDate |
2018-04-01 |
description |
While transforming growth factor-β (TGF-β) is known to be a key inducer of hepatic stellate cell (HSC) activation
during liver fibrosis but it is unclear which TGF-β receptor is required for this HSC-mediated fibrogenesis. Here, we report that
abrogation of TGF-β type I receptor ALK5 in HSC activation led to reduced collagen deposition and a decreased number of
myofibroblasts in livers of mutant mice lacking ALK5 in HSC (Alk5/GFAP-Cre mice) following thioacetamide (TAA) exposure.
The reduced fibrosis was accompanied by decreased expression of HSC activation markers in livers. In addition, Alk5/GFAP-Cre
mice exhibited decreased immune cell infiltration and reduced production of inflammatory cytokines. Associated with reduced
fibrosis and inflammation, amelioration of liver injury was observed in Alk5/GFAP-Cre mice after TAA treatment. In conclusion,
our results indicated that TGF-β signaling via ALK5 in HSC enhanced liver fibrogenesis and inflammation led to amplification
of hepatic injury in mice exposed to TAA. |
topic |
TGF-β ALK5 hepatic stellate cells fibrosis liver injury |
url |
http://rdo.psu.ac.th/sjstweb/journal/40-2/40-2-7.pdf |
work_keys_str_mv |
AT somyothsridurongrit abrogationofalk5inhepaticstellatecellsdecreaseshepaticfibrosisandamelioratesliverdamageinmicefollowingtreatmentwiththioacetamide AT chenke abrogationofalk5inhepaticstellatecellsdecreaseshepaticfibrosisandamelioratesliverdamageinmicefollowingtreatmentwiththioacetamide AT wanthitakongphat abrogationofalk5inhepaticstellatecellsdecreaseshepaticfibrosisandamelioratesliverdamageinmicefollowingtreatmentwiththioacetamide AT arnonpudgerd abrogationofalk5inhepaticstellatecellsdecreaseshepaticfibrosisandamelioratesliverdamageinmicefollowingtreatmentwiththioacetamide AT chanyatipsuwannasing abrogationofalk5inhepaticstellatecellsdecreaseshepaticfibrosisandamelioratesliverdamageinmicefollowingtreatmentwiththioacetamide |
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1725946820055531520 |