title: The ratio of transforming growth factor-β1/bone morphogenetic protein-7 in the progression of the epithelial-mesenchymal transition contributes to rat liver fibrosis.
abstract: This study was designed to show whether rat liver epithelial cells could undergo epithelial-mesenchymal transition (EMT), thereby directly contributing to liver fibrosis. The role of the ratio of transforming growth factor-β1 (TGF-β1)/bone morphogenetic protein-7 (BMP-7) was evaluated in the progression of EMT or mesenchymal-epithelial transition. Primary rat liver epithelial cells were stimulated with different ratios of TGF-β1/BMP-7 and examined for evidence of transition to a mesenchymal or epithelial phenotype. Liver sections were labeled to detect antigens associated with liver epithelial cells [E-cadherin (E-cad)], EMT [fibroblast-specific protein-1 (FSP-1), vimentin], myofibroblasts [α-smooth muscle actin (α-SMA)], and intracellular signal-transduction mediated by forming liver fibrosis undergo EMT, resulting in the formation of invasive fibroblasts; this process may be driven or impeded by a response to local TGF-β1 or BMP-7. BMP-7 downregulated α-SMA and phosphorylated Smad2/3. Stimulation of cultured cells with TGF-β1 induced the expression of pSmad2/3, FSP-1, and α-SMA. Stimulation of cultured cells with BMP-7 induced the expression of E-cad. We demonstrated that the cells upregulated E-cad release compared with untreated cells, but TGF-β1 was different. We found that the equilibrium of the ratio of TGF-β1/BMP-7 was 1/10. In summary, the mechanism for this process was not determined. Demonstration of the contribution of what the ratio of TGF-β1/BMP-7 induced to EMT to the chronic liver diseases would provide a new basis for understanding pathogenesis and potential treatment.
authors.affiliation: Department of Gastroenterology and Digestive Disease Institute, Tongji Hospital Branch, Tongji University School of Medicine, Shanghai, China.
authors.forename: W R
authors.initials: WR
authors.lastname: Bi
authors.affiliation: Department of Stem Cells Laboratory, Tongji University School of Medicine, Shanghai, China.
authors.forename: G T
authors.initials: GT
authors.lastname: Xu
authors.affiliation: Department of Stem Cells Laboratory, Tongji University School of Medicine, Shanghai, China.
authors.forename: L X
authors.initials: LX
authors.lastname: Lv
authors.affiliation: Department of Gastroenterology and Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China cqyang@tongji.edu.cn.
authors.forename: C Q
authors.initials: CQ
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000199:Actins; D055419:Bone Morphogenetic Protein 7; D015820:Cadherins; D002135:Calcium-Binding Proteins; D053773:Transforming Growth Factor beta1; C525821:Bmp7 protein, rat; C579666:FSP1 protein, rat; C508962:Tgfb1 protein, rat; C498862:Acta2 protein, rat