ß-catenin is overexpressed in hepatic fibrosis and blockage of Wnt/ß-catenin signaling inhibits hepatic stellate cell activation.
Mol Med Rep
; 9(6): 2145-51, 2014 Jun.
Article
in En
| MEDLINE
| ID: mdl-24691643
ABSTRACT
ß-catenin, a core component of Wnt/ß-catenin signaling, has been shown to be an important regulator of cellular proliferation and differentiation. Abnormal activation of Wnt/ß-catenin signaling promotes tissue fibrogenesis. In the present study, the role of ß-catenin during liver fibrogenesis was analyzed and the functional effects of ß-catenin gene silencing in hepatic stellate cells (HSCs) using small interfering (si)RNA were investigated. The expression of ß-catenin in human hepatic fibrosis tissues of different grades and normal human hepatic tissues was examined using immunohistochemistry. To inhibit the Wnt/ß-catenin signaling pathway, siRNA for ß-catenin was developed and transiently transfected into HSC-T6 cells using Lipofectamine 2000. ß-catenin expression was evaluated by quantitative polymerase chain reaction (qPCR) and western blot analysis. The expression of collagen types â
and â
¢ was evaluated by qPCR and immunofluorescent staining. Cellular proliferation and the cell cycle were analyzed using a methyl thiazolyl tetrazolium assay. Apoptosis was assessed by Annexin V staining. A higher expression level of ß-catenin was identified in the patients with high-grade hepatic fibrosis in comparison with that of the normal controls. Additionally, ß-catenin siRNA molecules were successfully transfected into HSCs and induced inhibition of ß-catenin expression in a time-dependent manner. ß-catenin siRNA treatment also inhibited synthesis of collagen types â
and â
¢ in transfected HSCs. Furthermore, compared with those of the control group, siRNA-mediated knockdown of ß-catenin in HSC-T6 cells inhibited cell proliferation and resulted in cell apoptosis. This study suggests a significant functional role for ß-catenin in the development of liver fibrosis and demonstrates that downregulation of the Wnt/ß-catenin signaling pathway inhibits HSC activation. Thus, this study provides a novel strategy for the treatment of hepatic fibrosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression
/
Beta Catenin
/
Hepatic Stellate Cells
/
Wnt Signaling Pathway
/
Liver Cirrhosis
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Med Rep
Year:
2014
Document type:
Article