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Updated: May 26, 2026
Heterotopic Auxiliary Whole Liver Rat Transplant Model Utilizing a Hepaticoureterostomy for Allograft Rejection Studies
Published on: March 8, 2024
Galectin-3 Promotes Graft Injury via NLRP3 Pyroptosis in Steatotic Liver Transplantation: A Therapeutic Target for
Xianwu Yang1, Shirui Huang1, Ruisi Ma1
1Department of Pediatric Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Background And Aims:
Steatotic donor livers are highly susceptible to post-transplant dysfunction; however, the underlying mechanisms remain incompletely understood. This study aimed to investigate the role of galectin-3 (LGALS3)-mediated pyroptosis in steatotic liver graft injury and explore its therapeutic potential.
Methods:
A mouse model of steatotic liver transplantation was established. Graft tissues were subjected to RNA sequencing to identify key regulators. In vitro, LGALS3 was modulated in steatotic hepatocytes under ischemia/reperfusion stress to assess its impact on the NLRP3 inflammasome and pyroptosis. The regulatory mechanism by which LGALS3 modulates NLRP3 ubiquitination was further examined. Finally, the therapeutic efficacy of LGALS3 inhibition was evaluated in an orthotopic liver transplantation model.
Results:
Transcriptomic analysis identified LGALS3 as a key upregulated molecule in steatotic grafts, associated with pyroptosis pathways. In vitro, LGALS3 overexpression enhanced NLRP3 inflammasome activation and pyroptotic cell death, whereas LGALS3 knockdown exerted protective effects. Mechanistically, LGALS3 modulated NLRP3 inflammasome activity by regulating its ubiquitination. In vivo, pharmacological inhibition of LGALS3 significantly improved graft function, reduced histological injury, suppressed pyroptosis, and prolonged recipient survival.
Conclusions:
This study demonstrates that LGALS3 drives steatotic graft injury by promoting NLRP3-mediated pyroptosis through the regulation of ubiquitination. These findings identify LGALS3 as a promising therapeutic target for improving the outcomes of liver transplantation using steatotic donor organs.
