Protein phosphatase type 2A (PP2A) is a large family of Ser/Thr phosphatases that provide the fine control on signaling pathway by governing the rate and duration of phosphorylation.The liver has enormous regenerative capacity, which stipulates the clinical outcome of a serious hepatic injury,cancer resection, and living donor liver transplantlation.In this study, we examined the expression paten of PP2Ac during liver regeneration, and found that both mRNA and protein level of PP2Ac increased markedly 4 days after PH.Following partial hepatectomy, the initiation and proliferation stage of liver regeneration in PP2Ac deleted mice remained similar to those in control mice, but the liver growth failed to stop properly at termination stage.The absence of PP2Ac activated the Akt-1 pathway and inhibited the degradation of CyclinD1 mediated by GSK3, thus promoted the transition of cell cycle and accelerated the proliferation of liver cells at the termination stage.The vigorous mitosis of hepatocytes in PP2Ac-/-livers finally resulted in 1.3-folds of original mass.These data indicate that PP2A(c)mediated signaling via Akt-1 and GSK3 is essential for proper termination of liver regeneration.In addition.Liver regeneration in a carbon tetrachloride (CC14)-induced liver is closer to pathologic state.PP2Acα-deficiency mice showed an increase about 30% of liver mass, after CC14 treatment compared with control.Furthermore, the expression of cyclin D1 and cyclin E, the two proliferation related genes, was significantly higher in PP2Aeα-deficient mice.Besides, elevated expression of hepatic α-SMA indicated activation of hepatic stellate cells, and in accordance,we detected some profibrogenic hepatic genes, such as Collagen I, TIMP-1,Fibronectin, the expression in PP2Acα-deficient mice is much lower.This prompts us that the knockout of PP2Acα has a protective effect on CCl4-induced liver injury, which is likely to be a brand-new therapeutically target for future treatment of liver fibrosis.Taken together, PP2Ac is crucially important to proper termination of liver regeneration, however, the absence of PP2Ac can protect liver from physical and chemical induction of damage.