title: Effect of alendronate sodium on the expression of mesenchymal-epithelial transition markers in mice with liver fibrosis.
abstract: The aim of this study was to explore whether alendronate sodium regulates tissue remodeling by controlling the transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) and bone morphogenetic protein (BMP)-7-induced mesenchymal-epithelial transition (MET) in CCl(4)-induced hepatic fibrosis in mice. A mouse model of CCl(4)-induced 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 TGF-β1, α-smooth muscle actin (α-SMA), BMP-7 and E-cadherin in the hepatic tissue was detected using immunohistochemistry. The mRNA and protein levels of TGF-β1, α-SMA, BMP-7, fibroblast-specific protein 1 (FSP1), E-cadherin and N-cadherin were detected using RT-PCR 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 TGF-β1 and α-SMA mRNA expression and increased BMP-7 and E-cadherin 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 TGF-β/smad- and BMP-7-modulated mechanisms which regulate EMT and MET in multifunctional progenitors.
authors.affiliation: Department of Gastroenterology and Digestive Disease Institute, Tongji Hospital Branch;
authors.forename: Wan-Rong
authors.initials: WR
authors.lastname: Bi
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Jin
authors.forename: Guo-Tong
authors.initials: GT
authors.lastname: Xu
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Yang