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Mest Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/β-Catenin Signaling Pathway

BACKGROUND/AIMS: The Wnt/β-catenin signaling pathway has been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesoderm-specific transcript homologue (Mest), a strong negative regulator of Wnt/β-catenin signaling, could inhibit liver fibrosis. METH...

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Autores principales: Li, Wenting, Zhu, Chuanlong, Li, Yi, Wu, Quan, Gao, Rentao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Gastroenterology; the Korean Society of Gastrointestinal Endoscopy; the Korean Association for the Study of the Liver; the Korean Society of Neurogastroenterology and Motility; Korean Association for the Study of Intestinal Diseases; Korean College of Helicobacter and Upper Gastrointestinal Research; Korean Pancreatobiliary Association; Korean Society of Gastrointestinal Cancer 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026646/
https://www.ncbi.nlm.nih.gov/pubmed/24827625
http://dx.doi.org/10.5009/gnl.2014.8.3.282
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author Li, Wenting
Zhu, Chuanlong
Li, Yi
Wu, Quan
Gao, Rentao
author_facet Li, Wenting
Zhu, Chuanlong
Li, Yi
Wu, Quan
Gao, Rentao
author_sort Li, Wenting
collection PubMed
description BACKGROUND/AIMS: The Wnt/β-catenin signaling pathway has been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesoderm-specific transcript homologue (Mest), a strong negative regulator of Wnt/β-catenin signaling, could inhibit liver fibrosis. METHODS: pcDNA-Mest was transfected into hepatic stellate cells (HSCs) and rats. Rats were randomly divided into four groups: normal group (normal saline), treatment group (pcDNA-Mest+CCl(4)), control group (pcDNA-neo+CCl(4)), and model group (normal saline+CCl(4)). Changes in liver pathology were evaluated by hematoxylin and eosin and Masson's trichrome staining. The levels of alanine transaminase, aspartate transaminase, lactic dehygrogenase, hyaluronic acid, and laminin in the serum and hydroxyproline in the liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of β-catenin, α-smooth muscle actin (α-SMA), Smad3, and tissue inhibitor of metalloproteinase type I were determined, and the viability of the HSCs was tested. RESULTS: Our data demonstrate that Mest alleviated CCl(4)-induced collagen deposition in liver tissue and improved the condition of the liver in rats. Mest also significantly reduced the expression and distribution of β-catenin, α-SMA and Smad3 both in vivo and in vitro, in addition to the viability of HSCs in vitro. CONCLUSIONS: We found that Mest attenuates liver fibrosis by repressing β-catenin expression, which provides a new therapeutic approach for treating liver fibrosis.
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spelling pubmed-40266462014-05-21 Mest Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/β-Catenin Signaling Pathway Li, Wenting Zhu, Chuanlong Li, Yi Wu, Quan Gao, Rentao Gut Liver Original Article BACKGROUND/AIMS: The Wnt/β-catenin signaling pathway has been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesoderm-specific transcript homologue (Mest), a strong negative regulator of Wnt/β-catenin signaling, could inhibit liver fibrosis. METHODS: pcDNA-Mest was transfected into hepatic stellate cells (HSCs) and rats. Rats were randomly divided into four groups: normal group (normal saline), treatment group (pcDNA-Mest+CCl(4)), control group (pcDNA-neo+CCl(4)), and model group (normal saline+CCl(4)). Changes in liver pathology were evaluated by hematoxylin and eosin and Masson's trichrome staining. The levels of alanine transaminase, aspartate transaminase, lactic dehygrogenase, hyaluronic acid, and laminin in the serum and hydroxyproline in the liver were detected by biochemical examination and radioimmunoassay, respectively. The expression and distribution of β-catenin, α-smooth muscle actin (α-SMA), Smad3, and tissue inhibitor of metalloproteinase type I were determined, and the viability of the HSCs was tested. RESULTS: Our data demonstrate that Mest alleviated CCl(4)-induced collagen deposition in liver tissue and improved the condition of the liver in rats. Mest also significantly reduced the expression and distribution of β-catenin, α-SMA and Smad3 both in vivo and in vitro, in addition to the viability of HSCs in vitro. CONCLUSIONS: We found that Mest attenuates liver fibrosis by repressing β-catenin expression, which provides a new therapeutic approach for treating liver fibrosis. The Korean Society of Gastroenterology; the Korean Society of Gastrointestinal Endoscopy; the Korean Association for the Study of the Liver; the Korean Society of Neurogastroenterology and Motility; Korean Association for the Study of Intestinal Diseases; Korean College of Helicobacter and Upper Gastrointestinal Research; Korean Pancreatobiliary Association; Korean Society of Gastrointestinal Cancer 2014-05 2013-12-24 /pmc/articles/PMC4026646/ /pubmed/24827625 http://dx.doi.org/10.5009/gnl.2014.8.3.282 Text en Copyright © 2014 by the Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association for the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Li, Wenting
Zhu, Chuanlong
Li, Yi
Wu, Quan
Gao, Rentao
Mest Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/β-Catenin Signaling Pathway
title Mest Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/β-Catenin Signaling Pathway
title_full Mest Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/β-Catenin Signaling Pathway
title_fullStr Mest Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/β-Catenin Signaling Pathway
title_full_unstemmed Mest Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/β-Catenin Signaling Pathway
title_short Mest Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/β-Catenin Signaling Pathway
title_sort mest attenuates ccl(4)-induced liver fibrosis in rats by inhibiting the wnt/β-catenin signaling pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4026646/
https://www.ncbi.nlm.nih.gov/pubmed/24827625
http://dx.doi.org/10.5009/gnl.2014.8.3.282
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