title: Hepatocyte-specific ablation of PP2A catalytic subunit α attenuates liver fibrosis progression via TGF-β1/Smad signaling.
abstract: Protein phosphatase 2A (PP2A), a family of the major serine/threonine phosphatases in cells, regulates many aspects of physiological processes. However, isoform-specific substrates and the biological role of each specific member of the PP2A family remain largely unknown. In this study, we investigated whether PP2A catalytic subunit Cα (PP2Acα) is involved in chronic hepatic injury and fibrosis. A hepatocyte-specific PP2Acα ablation mice model was established to examine the effect of PP2Acα on carbon tetrachloride- (CCl4-) induced chronic hepatic injury and fibrosis. Our results showed that PP2Acα knockout mice were less susceptible to chronic CCl4-induced liver injury as evidenced by lower levels of serum alanine aminotransferase and aspartate aminotransferase, decreased hepatocyte proliferation, and increased rate of apoptotic removal of the injured hepatocytes. PP2Acα knockout mice also displayed a lesser extent of liver fibrosis as a significant decrease in the proportion of α-smooth muscle actin-expressing cells and collagen deposition was observed in their liver tissues. Furthermore, the levels of serum TGF-β1 and hepatocytic Smad phosphorylation were reduced in the PP2Acα knockout mice. These data suggest that hepatocyte-specific ablation of PP2Acα protects against CCl4-induced chronic hepatic injury and fibrogenesis and the protective effect is mediated at least partially through the impaired TGF-β1/Smad signaling.
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Na
authors.identifier: 0000-0002-9075-2980
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Yun
authors.identifier: 0000-0002-4697-261X
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Model Animal Research Center of Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: An
authors.initials: A
authors.lastname: Tang
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Dengshun
authors.identifier: 0000-0002-2682-3502
authors.initials: D
authors.lastname: Miao
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xiaoqin
authors.identifier: 0000-0002-3084-5624
authors.initials: X
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018450:Disease Progression; D004789:Enzyme Activation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride; D054648:Protein Phosphatase 2