KODAMA Takahiro,TAKEHARA Tetsuoi ≪Gastroenterology and Hepatology≫ “Increases in p53 expression induce CTGF synthesis by mouse and human hepatocytes and result in liver fibrosis in mice”

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PublishJournal of Clinical Investigation; 121, 3343-56 (2011)

Chnonic hepatitis/Cirrhosis, which is characterized by liver fibrosis as its pathophysiology progresses to lethal liver failure or hepatocellular carcinoma. Herein, we have elucidated a novel link between p53, a pivotal tumor suppressor, activation in hepatocytes and liver fibrosis. Hepatocyte-specific disruption of Mdm2, promoting p53 degradation, led to p53-dependent spontaneous liver fibrosis. Hepatocyte-specific p53 deficiency decreased liver fibrosis in two models of liver fibrosis. As their underlying mechanism, we identified that p53 upregulated synthesis of CTGF, the hepatic fibrogenic master switch, via miRNA regulation. Moreover, human liver samples showed p53-CTGF pathway was correlated to the progression of human liver fibrosis. This study suggests that the p53/CTGF pathway may be a therapeutic target in the treatment of liver fibrosis.