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Mest Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/beta-Catenin Signaling Pathway
Gut and Liver ; : 282-291, 2014.
Article in En | WPRIM | ID: wpr-163239
Responsible library: WPRO
ABSTRACT
BACKGROUND/AIMS: The Wnt/beta-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/beta-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+CCl4), control group (pcDNA-neo+CCl4), and model group (normal saline+CCl4). 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 beta-catenin, alpha-smooth muscle actin (alpha-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 CCl4-induced collagen deposition in liver tissue and improved the condition of the liver in rats. Mest also significantly reduced the expression and distribution of beta-catenin, alpha-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 beta-catenin expression, which provides a new therapeutic approach for treating liver fibrosis.
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Full text: 1 Index: WPRIM Main subject: Carbon Tetrachloride / Transfection / Proteins / Random Allocation / Cells, Cultured / Rats, Wistar / Beta Catenin / Hepatic Stellate Cells / Wnt Signaling Pathway / Liver Cirrhosis, Experimental Limits: Animals Language: En Journal: Gut and Liver Year: 2014 Type: Article
Full text: 1 Index: WPRIM Main subject: Carbon Tetrachloride / Transfection / Proteins / Random Allocation / Cells, Cultured / Rats, Wistar / Beta Catenin / Hepatic Stellate Cells / Wnt Signaling Pathway / Liver Cirrhosis, Experimental Limits: Animals Language: En Journal: Gut and Liver Year: 2014 Type: Article