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BioMed Research International
Volume 2015 (2015), Article ID 794862, 10 pages
Research Article

Hepatocyte-Specific Ablation of PP2A Catalytic Subunit α Attenuates Liver Fibrosis Progression via TGF-β1/Smad Signaling

1Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, China
2Model Animal Research Center of Nanjing University, Nanjing, Jiangsu 210061, China

Received 1 September 2014; Revised 18 November 2014; Accepted 18 November 2014

Academic Editor: Yury Popov

Copyright © 2015 Na Lu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.