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Urantide alleviates lipopolysaccharide/D-galactosamine-induced acute liver failure through upregulating
Wanhua Yang1, Shu Bian1, Liangming Liu1
1Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Aims:
To investigate the effect of urotensin II(UII)/UII receptor(UT) on hepatic carboxylesterase1f(Ces1f) expression in acute liver failure(ALF) mice.
Methods:
ALF was induced in male Balb/c mice using lipopolysaccharide (LPS)/D-galactosamine (D-GalN) i.p. after a tail vein injection of Urantide, a specific antagonist of UT receptor. Liver tissues were collected at 0-12h to detect UII and Ces1f mRNA levels in ALF mice. Mice were divided into four groups (n=6 each group): (A) Urantide(-), LPS/D-GalN(-), (B) Urantide(+), LPS/D-GalN(-), (C) Urantide(-), LPS/D-GalN(+), and (D) Urantide(+), LPS/D-GalN(+). Liver tissues were collected at 6 h after a challenge of LPS/D-GalN. Time-depended levels were observed of hepatic UII and Ces1f mRNA over a period of 12 hours after LPS/D-GalN challenge. Liver injury was evaluated via hematoxylin-eosin (HE) staining, serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST), and the mRNA and protein expression levels of Ces1f and UII expression were determined by fluorescence in situ hybridization(FISH), quantitative real-time PCR (qPCR) and Western blotting (WB), respectively.
Results:
After LPS/D-GalN injection, hepatic UII mRNA rose at 2 h (P < 0.05 vs 0 h), reached the peaked level at 6 h, and the level began to degrade at 8 h, but remained higher than at 0 h (P < 0.05, 10 h vs 0 h) till 12 h (P>0.05, 12 h vs 0 h); while hepatic Ces1f mRNA decreased at 6 h (P < 0.05 vs 0 h), reached the lowest level at 10 h, but began to rise at 12 h (P>0.05, 12 h vs 10 h). In addition, urantide pretreatment inhibited the up-regulated expressions of hepatic UII mRNA and protein, whereas increases the down-regulated expressions of hepatic Ces1f mRNA and protein induced by LPS/D-GalN attack at 6 h.And serum ALT and AST levels were significantly decreased, whereas hepatic inflammatory injury improved via urantide injection in LPS/D-GalN-induced ALF mice.
Conclusion:
Ces1f maybe negatively regulated by UII/UT signal in LPS/D-GalN-induced ALF.
