ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
This article is part of the Research TopicInter-organ Dynamics in Health and Disease: From the Gut–Liver Axis to the Gut–Liver–X AxisView all articles
TCDCA inhibits pyroptosis to alleviate sepsis-related acute Hepatic injury via activating TGR5
Provisionally accepted
- 1Jinzhou Medical University, Shanghai east Hospital, Shanghai, China
- 2Shanghai East Hospital, Tongji University School of Medicine, shanghai, China
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Sepsis-related acute hepatic injury (SALI) is a life - threatening complication in septic patients, and current treatments have limited efficacy. This study investigated the role of taurochenodeoxycholic acid (TCDCA) in SALI using a cecal ligation and puncture (CLP) mouse model. TCDCA treatment significantly reduced serum levels of liver injury markers (AST and ALT), suppressed pro - inflammatory cytokines (IL-6, TNF-α, IL-1β), and alleviated histological damage, including lobular disruption, inflammation, and hemorrhage. TCDCA also decreased hepatocyte apoptosis and modulated the liver macrophage response. Molecular docking showed a strong interaction between TCDCA and G protein - coupled bile acid receptor 1 (TGR5), and the TGR5 antagonist SBI-115 abolished TCDCA's protective effects. Transcriptomic analysis identified 430 differentially expressed genes after TCDCA treatment, with enrichment in pyroptosis - related pathways. Western blot analysis confirmed that TCDCA inhibited the activation of NLRP3 inflammasome and downstream pyroptotic proteins, an effect reversed by SBI - 115. These results indicate that TCDCA protects against SALI by suppressing hepatocyte pyroptosis via TGR5. While these findings highlight TCDCA as a potential therapeutic for SALI, further research, including clinical trials, is needed to address species - specific differences and fully elucidate its mechanisms of action.
Keywords: Sepsis, Acute hepatic injury, Taurochenodeoxycholic Acid, tgr5, Hepatocyte pyroptosis
Received: 15 Sep 2025; Accepted: 11 Nov 2025.
Copyright: © 2025 Yang, Rong, Li, Wang, Liu, Wang and Liao. 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:
Zetian Wang, 2411239@tongji.edu.cn
Lijun Liao, liao@pan-support.com
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