Inhibiting the expression of hepatocyte nuclear factor 4 alpha attenuates lipopolysaccharide/D-galactosamine-induced fulminant hepatic failure in mice.

Abstract

BACKGROUND:

Hepatocyte nuclear factor 4 alpha (HNF4alpha) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4alpha in the development of fulminant hepatic failure (FHF) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN).

METHODS:

The FHF model was induced by simultaneous intraperitoneal injection of LPS/D-GalN in mice. Three days prior to LPS/D-GalN administration, HNF4alpha short-hairpin interfering RNA expression plasmid or physiological saline was injected via the tail vein with a hydrodynamics-based procedure. The degree of hepatic damage and cumulative survival rate were subsequently assessed.

RESULTS:

The expression of HNF4alpha was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4alpha reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated histological injury, and improved the survival of mice with FHF. In addition, both serum and hepatic tumor necrosis factor alpha expression were suppressed when HNF4alpha expression was inhibited in mice with FHF.

CONCLUSION:

Inhibiting HNF4alpha expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.

• Authors: En-Qiang Chen, Dao-Yin Gong, Xiao-Hua Leng, Lang Bai, Cong Liu, Li-Chun Wang, Hong Tang
• Journal: Hepatobiliary & pancreatic diseases international : HBPD INT (Hepatobiliary Pancreat Dis Int) Vol. 11 Issue 6 Pg. 624-9 (Dec 15 2012) ISSN: 1499-3872 [Print] Singapore
• PMID: 23232634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hepatocyte Nuclear Factor 4
• Hnf4a protein, mouse
• Lipopolysaccharides
• RNA, Messenger
• RNA, Small Interfering
• Tumor Necrosis Factor-alpha
• Galactosamine
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Disease Models, Animal
• Galactosamine
• Hepatocyte Nuclear Factor 4 (genetics, metabolism)
• Lipopolysaccharides
• Liver Failure, Acute (blood, chemically induced, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Plasmids
• RNA, Messenger (metabolism)
• RNA, Small Interfering
• Survival Rate
• Transfection
• Tumor Necrosis Factor-alpha (blood, genetics, metabolism)