Gut Liver.  2014 May;8(3):282-291.

Mest Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/beta-Catenin Signaling Pathway

• Li W
• Zhu C
• Li Y
• Wu Q
• Gao R

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.

Keyword

Mesoderm-specific transcript homologue; Liver cirrhosis; Wnt/beta-catenin; Hepatic stellate cell

MeSH Terms

Animals
Carbon Tetrachloride/toxicity
Cells, Cultured
Hepatic Stellate Cells/physiology
Liver Cirrhosis, Experimental/*physiopathology
Male
Proteins/*physiology
Random Allocation
Rats, Wistar
Transfection
Wnt Signaling Pathway/*physiology
beta Catenin/metabolism
Carbon Tetrachloride
Proteins
beta Catenin