Urantide alleviates lipopolysaccharide/D-galactosamine-induced acute liver failure - Aims, methods, results and conclusion

Sep 28, 2026

Acute liver failure (ALF) involves severe hepatic injury that disrupts detoxification and metabolic functions, driven in part by inflammatory signaling from hepatic immune cells. This study evaluated how urantide modulates the urotensin II (UII)/UII receptor (UT) axis and hepatic carboxylesterase 1f (Ces1f) expression in LPS/D-galactosamine-induced ALF mice. Male Balb/c mice received urantide prior to challenge; liver UII and Ces1f mRNA were followed from 0 to 12 h alongside injury assessment. Results showed urantide altered UII/UT and Ces1f expression patterns and reduced ALT/AST with improved inflammatory injury.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Acute liver failure and hepatic immune inflammation

Urotensin II (UII) and UII receptor (UT)

Methods

Results

Conclusion

TYPE Original Research PUBLISHED 17 December 2025 DOI 10.3389/fcimb.2025.1653725 OPEN ACCESS EDITED BY Jake J Wen, University of Texas Medical Branch at Galveston, United States REVIEWED BY Hanwei Jiao, Southwest University, China Shruti Ahlawat, Shree Guru Gobind Singh Tricentenary University, India *CORRESPONDENCE Liangming Liu [liuliangming@shsmu.edu.cn](liuliangming@shsmu.edu.cn) †These author shave contributed equally to this work and share ﬁrst authorship RECEIVED 29 August 2025 REVISED 17 November 2025 ACCEPTED 28 November 2025 PUBLISHED 17 December 2025 CITATION Yang W, Bian S and Liu L (2025) Urantide alleviates lipopolysaccharide/Dgalactosamine-induced acute liver failure through upregulating carboxylesterase1f in mice. Front. Cell. Infect. Microbiol. 15:1653725 . doi: 10.3389/fcimb.2025.1653725 COPYRIGHT © 2025 Yang, Bian and Liu. This is an openaccess 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) and the copyright owner(s) 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. Urantide alleviateslipopolysaccharide/Dgalactosamine-induced acute liver failure through upregulating carboxylesterase1f in mice Wanhua Yang †, Shu Bian † and Liangming Liu* Songjiang 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 Ces1fmRNA 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-GalNinduced ALF. KEYWORDS acute liver failure, urotensin II, UII receptor, Ces1f, mouse Frontiers in Cellular and Infection Microbiology 01 [frontiersin.org](frontiersin.org) 1 Introduction Acute liver failure (ALF) is an acute onset condition characterized by severe liver damage caused by multiple factors, leading to signiﬁcant impairment or decompensation of the

FAQs

What research question does the study address?

The study investigates how urantide affects UII/UT-regulated hepatic carboxylesterase 1f (Ces1f) expression in acute liver failure mice.

How was acute liver failure induced and how was urantide administered?

ALF was induced in male Balb/c mice using lipopolysaccharide (LPS)/D-galactosamine (D-GalN) after a tail vein injection of urantide, a UT receptor antagonist.

What were the key findings regarding UII and Ces1f expression?

After LPS/D-GalN, hepatic UII mRNA rose and peaked at 6 h, while Ces1f mRNA decreased at 6 h and reached its lowest point later before increasing at 12 h. Urantide pretreatment inhibited UII upregulation and countered the D-GalN-induced downregulation of Ces1f at both mRNA and protein levels.

Sep 28, 2026

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