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

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.
(Hepatobiliary Pancreat Dis Int 2012;11:624-629)