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Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling

The acute liver disease is involved in aberrant release of high-mobility group box 1 (HMGB1). Glycyrrhizin (GL), a traditional Chinese medicine for liver disease, binds to HMGB1, thereby inhibits tissue injury. However the mode of action of GL for chronic liver disease remains unclear. We investigat...

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Autores principales: Morita, Akihiro, Omoya, Yuta, Ito, Rie, Ishibashi, Yuya, Hiramoto, Keiichi, Ohnishi, Shiho, Yoshikawa, Nobuji, Kawanishi, Shosuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654616/
https://www.ncbi.nlm.nih.gov/pubmed/34934826
http://dx.doi.org/10.1016/j.bbrep.2021.101181
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author Morita, Akihiro
Omoya, Yuta
Ito, Rie
Ishibashi, Yuya
Hiramoto, Keiichi
Ohnishi, Shiho
Yoshikawa, Nobuji
Kawanishi, Shosuke
author_facet Morita, Akihiro
Omoya, Yuta
Ito, Rie
Ishibashi, Yuya
Hiramoto, Keiichi
Ohnishi, Shiho
Yoshikawa, Nobuji
Kawanishi, Shosuke
author_sort Morita, Akihiro
collection PubMed
description The acute liver disease is involved in aberrant release of high-mobility group box 1 (HMGB1). Glycyrrhizin (GL), a traditional Chinese medicine for liver disease, binds to HMGB1, thereby inhibits tissue injury. However the mode of action of GL for chronic liver disease remains unclear. We investigated the effects of glycyrrhizin (GL) and its derivatives on liver differentiation using human iPS cells by using a flow cytometric analysis. GL promoted hepatic differentiation at the hepatoblast formation stage. The GL derivatives, 3-O-mono-glucuronyl 18β-glycyrrhetinic acid (Mono) and 3-O-[glucosyl (1 → 2)-glucuronyl] 18β-glycyrrhetinic acid increased AFP(+) cell counts and albumin(+) cell counts. Glucuronate conjugation seemed to be a requirement for hepatic differentiation. Mono exhibited the most significant hepatic differentiation effect. We evaluated the effects of (±)-2-(2,4-dichlorophenoxy) propionic acid (DP), a T1R3 antagonist, and sucralose, a T1R3 agonist, on hepatic differentiation, and found that DP suppressed Mono-induced hepatic differentiation, while sucralose promoted hepatic differentiation. Thus, GL promoted hepatic differentiation via T1R3 signaling. In addition, Mono increased β-catenin(+) cell count and decreased Hes5(+) cell count suggesting the involvement of Wnt and Notch signaling in GL-induced hepatic differentiation. In conclusion, GL exerted a hepatic differentiation effect via sweet receptor (T1R3), canonical Wnt, and Notch signaling.
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spelling pubmed-86546162021-12-20 Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling Morita, Akihiro Omoya, Yuta Ito, Rie Ishibashi, Yuya Hiramoto, Keiichi Ohnishi, Shiho Yoshikawa, Nobuji Kawanishi, Shosuke Biochem Biophys Rep Research Article The acute liver disease is involved in aberrant release of high-mobility group box 1 (HMGB1). Glycyrrhizin (GL), a traditional Chinese medicine for liver disease, binds to HMGB1, thereby inhibits tissue injury. However the mode of action of GL for chronic liver disease remains unclear. We investigated the effects of glycyrrhizin (GL) and its derivatives on liver differentiation using human iPS cells by using a flow cytometric analysis. GL promoted hepatic differentiation at the hepatoblast formation stage. The GL derivatives, 3-O-mono-glucuronyl 18β-glycyrrhetinic acid (Mono) and 3-O-[glucosyl (1 → 2)-glucuronyl] 18β-glycyrrhetinic acid increased AFP(+) cell counts and albumin(+) cell counts. Glucuronate conjugation seemed to be a requirement for hepatic differentiation. Mono exhibited the most significant hepatic differentiation effect. We evaluated the effects of (±)-2-(2,4-dichlorophenoxy) propionic acid (DP), a T1R3 antagonist, and sucralose, a T1R3 agonist, on hepatic differentiation, and found that DP suppressed Mono-induced hepatic differentiation, while sucralose promoted hepatic differentiation. Thus, GL promoted hepatic differentiation via T1R3 signaling. In addition, Mono increased β-catenin(+) cell count and decreased Hes5(+) cell count suggesting the involvement of Wnt and Notch signaling in GL-induced hepatic differentiation. In conclusion, GL exerted a hepatic differentiation effect via sweet receptor (T1R3), canonical Wnt, and Notch signaling. Elsevier 2021-12-04 /pmc/articles/PMC8654616/ /pubmed/34934826 http://dx.doi.org/10.1016/j.bbrep.2021.101181 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Morita, Akihiro
Omoya, Yuta
Ito, Rie
Ishibashi, Yuya
Hiramoto, Keiichi
Ohnishi, Shiho
Yoshikawa, Nobuji
Kawanishi, Shosuke
Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling
title Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling
title_full Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling
title_fullStr Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling
title_full_unstemmed Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling
title_short Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling
title_sort glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, wnt, and notch signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654616/
https://www.ncbi.nlm.nih.gov/pubmed/34934826
http://dx.doi.org/10.1016/j.bbrep.2021.101181
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