ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Clinical and Diagnostic Microbiology and Immunology
Urantide Alleviates Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure Through Upregulating Carboxylesterase1f In Mice
Provisionally accepted
- 1Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 2Shanghai Songjiang Clinical Medical College of Nanjing Medical University, Shanghai, China
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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.
Keywords: Acute liver failure1, Urotensin II2, UII receptor3, Ces1f4, mouse5
Received: 29 Aug 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Yang, Bian and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Liangming Liu
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