Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide
© 2018, Prince of Songkla University. All rights reserved. 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 th...
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th-mahidol.475282019-08-28T14:13:23Z Abrogation of ALK5 in hepatic stellate cells decreases hepatic fibrosis and ameliorates liver damage in mice following treatment with thioacetamide Somyoth Sridurongrit Chen Ke Wanthita Kongphat Arnon Pudgerd Chanyatip Suwannasing Mahidol University Multidisciplinary © 2018, Prince of Songkla University. All rights reserved. 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. 2019-08-28T07:13:23Z 2019-08-28T07:13:23Z 2018-03-01 Article Songklanakarin Journal of Science and Technology. Vol.40, No.2 (2018), 314-320 10.14456/sjst-psu.2018.31 01253395 2-s2.0-85048337768 https://repository.li.mahidol.ac.th/handle/123456789/47528 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85048337768&origin=inward |
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Multidisciplinary 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 |
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© 2018, Prince of Songkla University. All rights reserved. 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. |
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Mahidol University |
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Mahidol University Somyoth Sridurongrit Chen Ke Wanthita Kongphat Arnon Pudgerd Chanyatip Suwannasing |
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Article |
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Somyoth Sridurongrit Chen Ke Wanthita Kongphat Arnon Pudgerd Chanyatip Suwannasing |
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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 |
publishDate |
2019 |
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https://repository.li.mahidol.ac.th/handle/123456789/47528 |
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1763495865396232192 |