The inhibitory action of PDCD4 in lipopolysaccharide/D-galactosamine-induced acute liver injury.

Abstract

Programmed cell death 4 (PDCD4) acts as a tumor suppressor gene, which suppresses tumor growth, infiltration and metastasis. Our previous studies demonstrated that PDCD4 had an important role in the development of ovarian cancer and glioma. Recent studies show that PDCD4 is also involved in various inflammatory diseases. However, its exact effect on inflammation remains unclear. In our current study, we explored the role of PDCD4 in acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) using wild-type (WT) mice and PDCD4-deficient mice. Our results showed that liver-to-body weight ratios, as well as serum aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly increased in PDCD4-deficient mice than WT mice. Histological examination, immunohistochemical and TUNEL analysis revealed PDCD4-deficient mice had more necrotic and apoptotic hepatocytes, inflammatory cells infiltration and liver internal hemorrhage than WT mice. In addition, some inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in the serum and liver tissues were also significantly increased in PDCD4-deficient mice. More importantly, we found that the aggravation of liver tissue injury in PDCD4-deficient mice was due to excessive mitogen-activated protein kinase and NF-κB activation, which induced the release of more inflammatory factors, and consequently resulted in higher levels of hepatocyte necrosis and apoptosis. These results indicate that PDCD4 has a protective role in LPS/D-GalN-induced acute liver injury. This finding may present new opportunities for PDCD4 to be explored as a therapeutic target in acute liver injury.

• Authors: Xiaoyan Wang, Lining Zhang, Zengtao Wei, Xia Zhang, Qi Gao, Yanyan Ma, Xingli Liu, Yang Jiang, Xianglan Liu, Chun Guo, Xiaoyan Wang
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 93 Issue 3 Pg. 291-302 (Mar 2013) ISSN: 1530-0307 [Electronic] United States
• PMID: 23295647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• Pdcd4 protein, mouse
• RNA-Binding Proteins
• Tumor Necrosis Factor-alpha
• Galactosamine
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Apoptosis Regulatory Proteins (deficiency, metabolism)
• Aspartate Aminotransferases (blood)
• Chemical and Drug Induced Liver Injury (genetics, pathology)
• Galactosamine (toxicity)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Interleukin-6 (blood)
• Lipopolysaccharides (toxicity)
• Liver (pathology)
• Mice
• NF-kappa B (metabolism)
• Organ Size
• RNA-Binding Proteins (metabolism)
• Tumor Necrosis Factor-alpha (blood)