Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease

Panasiuk, Anatol; Dzięcioł, J; Panasiuk, Bozena; Prokopowicz, D

doi:10.3748/wjg.v12.i38.6198

Cited by 103 publications

(85 citation statements)

References 21 publications

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“…A recent report showed that p53 activation correlated with susceptibility to ethanol-induced liver damage, a pathologic condition that is thought to mechanistically resemble NASH [20]. In addition, hepatic p53 expression and hepatocyte apoptosis increase in patients with NASH and a mouse model of NASH [7,8]. These results suggest that p53 plays a role in the pathophysiology of NASH, although the precise contributions have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Reactive oxygen species (ROS), which are thought to make major contributions to aging, stimulate p53 stabilization and subsequent induction of apoptosis via a feed-forward regulatory loop [6]. Hepatic p53 expression is elevated in patients with NASH [7]. A recent report has also shown that hepatic p53 expression and hepatocyte apoptosis significantly increase in a mouse model of NASH [8].…”

Section: Introductionmentioning

confidence: 99%

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p53/p66Shc-mediated signaling contributes to the progression of non-alcoholic steatohepatitis in humans and mice

Tomita

Teratani

Suzuki

et al. 2012

Journal of Hepatology

103

105

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

p53/p66Shc-mediated signaling contributes to the progression of non-alcoholic steatohepatitis in humans and mice

Tomita

Teratani

Suzuki

et al. 2012

Journal of Hepatology

103

105

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“…The molecular mechanism of organ fibrosis has not yet been comprehensively clarified due to its complexity, and thus far, whether p53 is directly involved in its pathophysiology has not been addressed. Recently, p53 has been shown to accumulate in hepatocytes of several fibrotic liver diseases, such as non-alcoholic steatohepatitis (NASH) (8,9), viral hepatitis (10,11), and primary biliary cirrhosis (PBC) (12). However, the precise role of p53 in liver fibrosis is unclear.…”

Section: Introductionmentioning

confidence: 99%

Increases in p53 expression induce CTGF synthesis by mouse and human hepatocytes and result in liver fibrosis in mice

et al. 2011

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The tumor suppressor p53 has been implicated in the pathogenesis of non-cancer-related conditions such as insulin resistance, cardiac failure, and early aging. In addition, accumulation of p53 has been observed in the hepatocytes of individuals with fibrotic liver diseases, but the significance of this is not known. Herein, we have mechanistically linked p53 activation in hepatocytes to liver fibrosis. Hepatocyte-specific deletion in mice of the gene encoding Mdm2, a protein that promotes p53 degradation, led to hepatocyte synthesis of connective tissue growth factor (CTGF; the hepatic fibrogenic master switch), increased hepatocyte apoptosis, and spontaneous liver fibrosis; concurrent removal of p53 completely abolished this phenotype. Compared with wild-type controls, mice with hepatocyte-specific p53 deletion exhibited similar levels of hepatocyte apoptosis but decreased liver fibrosis and hepatic CTGF expression in two models of liver fibrosis. The clinical significance of these data was highlighted by two observations. First, p53 upregulated CTGF in a human hepatocellular carcinoma cell line by repressing miR-17-92. Second, human liver samples showed a correlation between CTGF and p53-regulated gene expression, which were both increased in fibrotic livers. This study reveals that p53 induces CTGF expression and promotes liver fibrosis, suggesting that the p53/CTGF pathway may be a therapeutic target in the treatment of liver fibrosis.

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“…Other work has observed that the inflammation in human liver that occurs with NAFLD and NASH is paralleled with increases in p53 [76]. This has also been supported by p53 activation of mitochondrial pathways of apoptosis in an animal model of NASH [77].…”

Section: Mir-34amentioning

confidence: 78%

Recent Advances in Understanding of NASH: MicroRNAs as Both Biochemical Markers and Players

Vincent¹,

Sanyal²

2014

Curr Pathobiol Rep

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Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatis (NASH) are becoming the dominant liver diseases in the US and Western World. Extensive work is being done to diagnose, understand, and explore the pathogenesis of these multivariable complex diseases. Recently a new avenue of biologic regulation is being explored. MicroRNAs are non-coding RNAs that modulate the expression of multiple genes and have been implicated in multiple diseases. Recently there is a growing body of evidence supporting a significant role of microRNAs in NAFLD pathogenesis and progression to NASH, and hinting at their use as targets, biomarkers and potential therapeutic tools. This review is designed to highlight some of the recent work on a few of the key microRNAs involved in the pathogenesis of NAFLD and NASH.

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Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease

Abstract: Apoptosis is one of the most important mechanisms leading to hepatocyte elimination in NAFLD. The intensification of inflammation in NAFLD induces proapoptotic protein p53 with the inhibition of antiapoptotic Bcl-2.

Cited by 103 publications

References 21 publications

p53/p66Shc-mediated signaling contributes to the progression of non-alcoholic steatohepatitis in humans and mice

p53/p66Shc-mediated signaling contributes to the progression of non-alcoholic steatohepatitis in humans and mice

Increases in p53 expression induce CTGF synthesis by mouse and human hepatocytes and result in liver fibrosis in mice

Recent Advances in Understanding of NASH: MicroRNAs as Both Biochemical Markers and Players

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