Mest Attenuates CCl4-Induced Liver Fibrosis in Rats by Inhibiting the Wnt/ β-Catenin Signaling Pathway
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Background/Aims: The Wnt/β-catenin signaling pathwayhas been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesodermspecifictranscript homologue (Mest), a strong negative regulatorof Wnt/β-catenin signaling, could inhibit liver fibrosis. Methods: pcDNA-Mest was transfected into hepatic stellatecells (HSCs) and rats. Rats were randomly divided into fourgroups: normal group (normal saline), treatment group (pcDNA-Mest+CCl4), control group (pcDNA-neo+CCl4), and modelgroup (normal saline+CCl4). Changes in liver pathology wereevaluated by hematoxylin and eosin and Masson’s trichromestaining. The levels of alanine transaminase, aspartate transaminase,lactic dehygrogenase, hyaluronic acid, and lamininin the serum and hydroxyproline in the liver were detectedby biochemical examination and radioimmunoassay, respectively. The expression and distribution of β-catenin, α-smoothmuscle actin (α-SMA), Smad3, and tissue inhibitor of metalloproteinasetype I were determined, and the viability of theHSCs was tested. Results: Our data demonstrate that Mestalleviated CCl4-induced collagen deposition in liver tissue andimproved the condition of the liver in rats. Mest also significantlyreduced the expression and distribution of β-catenin,α-SMA and Smad3 both in vivo and in vitro , in addition to theviability of HSCs in vitro. Conclusions: We found that Mestattenuates liver fibrosis by repressing β-catenin expression,which provides a new therapeutic approach for treating liverfibrosis.
Abstract
Background/Aims: The Wnt/β-catenin signaling pathwayhas been reported to play an important role in liver fibrosis. This study was designed to investigate whether mesodermspecifictranscript homologue (Mest), a strong negative regulatorof Wnt/β-catenin signaling, could inhibit liver fibrosis. Methods: pcDNA-Mest was transfected into hepatic stellatecells (HSCs) and rats. Rats were randomly divided into fourgroups: normal group (normal saline), treatment group (pcDNA-Mest+CCl4), control group (pcDNA-neo+CCl4), and modelgroup (normal saline+CCl4). Changes in liver pathology wereevaluated by hematoxylin and eosin and Masson’s trichromestaining. The levels of alanine transaminase, aspartate transaminase,lactic dehygrogenase, hyaluronic acid, and lamininin the serum and hydroxyproline in the liver were detectedby biochemical examination and radioimmunoassay, respectively. The expression and distribution of β-catenin, α-smoothmuscle actin (α-SMA), Smad3, and tissue inhibitor of metalloproteinasetype I were determined, and the viability of theHSCs was tested. Results: Our data demonstrate that Mestalleviated CCl4-induced collagen deposition in liver tissue andimproved the condition of the liver in rats. Mest also significantlyreduced the expression and distribution of β-catenin,α-SMA and Smad3 both in vivo and in vitro , in addition to theviability of HSCs in vitro. Conclusions: We found that Mestattenuates liver fibrosis by repressing β-catenin expression,which provides a new therapeutic approach for treating liverfibrosis.
참고문헌 (25)
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