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| Inhibiting the expression of hepatocyte nuclear factor 4 alpha attenuates lipopolysaccharide/D-galactosamine-induced fulminant hepatic failure in mice |
| En-Qiang Chen, Dao-Yin Gong, Xiao-Hua Leng, Lang Bai, Cong Liu, Li-Chun Wang and Hong Tang |
Chengdu, China
Author Affiliations: Center for Infectious Diseases, West China Hospital and State Key Laboratory of Biotherapy (Chen EQ, Leng XH, Bai L, Liu C, Wang LC and Tang H); Department of Forensic Pathology, College of Basic Medicine and Forensic Medicine (Gong DY), Sichuan University, Chengdu 610041, China
Corresponding Author: Hong Tang, MD, Center for Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China (Tel: 86-28-85422650; Fax: 86-28-85422650; Email: htang6198@hotmail.com) |
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Abstract BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α 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, HNF4α 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 HNF4α was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4α 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 HNF4α expression was inhibited in mice with FHF.
CONCLUSION: Inhibiting HNF4α expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.
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2012, Vol. 11 
