Publisher： Spandidos Publications
ISSN： 1792-0981
Source： Experimental and Therapeutic Medicine, Vol.5, Iss.1, 2013-01, pp. : 247-252
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Abstract
The aim of this study was to explore whether alendronate sodium regulates tissue remodeling by controlling the transforming growth factor (TGF)β1induced epithelialmesenchymal transition (EMT) and bone morphogenetic protein (BMP)7induced mesenchymalepithelial transition (MET) in CCl4induced hepatic fibrosis in mice. A mouse model of CCl4induced hepatic fibrosis was evaluated using the hematoxylin and eosin (HE) and Masson's trichrome staining histological methods. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automated biochemical analyzer. The expression of TGFβ1, αsmooth muscle actin (αSMA), BMP7 and Ecadherin in the hepatic tissue was detected using immunohistochemistry. The mRNA and protein levels of TGFβ1, αSMA, BMP-7, fibroblast-specific protein 1 (FSP1), E-cadherin and N-cadherin were detected using RTPCR and western blot analysis. Immunohistochemical and molecular biochemical examination revealed that alendronate sodium significantly arrested the progression of hepatic fibrosis. Alendronate sodium caused significant amelioration of liver injury and reduced the activities of serum ALT and AST (P<0.001). Furthermore, alendronate sodium markedly reduced TGFβ1 and αSMA mRNA expression and increased BMP7 and Ecadherin in the mouse liver tissue (P<0.001). Alendronate sodium significantly arrested the progression of hepatic fibrosis. The underlying mechanism was associated with changes in the redox state, which remains variable in liver fibrosis, and depends on the balance between TGFβ/smad and BMP7modulated mechanisms which regulate EMT and MET in multifunctional progenitors.
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