Recently, researchers from Japan's Keio University School of Medicine, p53/p66Shc mediated signaling promotes the development of IL29 non-alcoholic steatohepatitis (NASH) in humans and mice. Related research published online in the Journal of Hepatology June 3. p53 is a tumor suppressor gene is a negative regulator of cell cycle and cell cycle regulation, DNA repair, cell differentiation, apoptosis, the important biological functions. p53 gene mutation (deletion) is the common events of human IL2RA tumors and tumor occurrence, development-related. Is generally believed that p53 over-expression and tumor metastasis, recurrence and poor prognosis. In this study, in order to clarify the role of p53 in non-alcoholic steatohepatitis, the researchers give the wild-type and p53-deficient male rats to a lack of methionine and choline food, eight weeks of continuous feeding induced IL2RB nutritional steatohepatitis model. They then assessed the normal liver tissue and non-alcoholic liver disease (NAFLD) in patients with mRNA expression profiles.
The study found that in the mouse NASH model in vivo,Il2rg liver cells, p53 and p66Shc signal enhancement. P53-deficient inhibition of p66Shc signal enhanced, reducing the number of intrahepatic lipid peroxidation and apoptosis in liver cells and improve the nutritional steatohepatitis. In primary cultured liver cells, transforming growth factor (TGF)-β in treatment, they found that the increase in p53 and p66Shc signal, resulting in a significant reactive oxygen IL3 species (ROS) accumulation and apoptosis. P53-deficient inhibition of TGF-β-induced p66Shc signal ROS accumulation, and liver cell apoptosis. In addition, in contrast to normal liver tissue specimens, human NAFLD liver samples of p53 and of p21 and the p66Shc the expression level was significantly improved. In patients with NAFLD, compared with simple steatosis groups, people with NASH have higher intrahepatic of p53, the level of expression of p21 and p66Shc. This indicates that there is a significant association between the expression levels of p53 and p66Sh. Overall, in liver cells, p53 control p66Shc signal level of ROS and apoptosis, regulating the progress of steatohepatitis. Moreover, these processes are likely to be involved in the regulation of TGF-β. In addition, Toshifumi Hibi, the results show that p53/p66Shc will be able to become a potential target for treatment of nonalcoholic steatohepatitis.