Related Experiment Video
Updated: May 29, 2025
Use of a Hanging-weight System for Liver Ischemia in Mice
Published on: August 7, 2012
SENP2 as a critical regulator in liver ischemia-reperfusion injury
Lei Zheng1, Shuling Han2, Olivia M Martinez2
1Transplant Immunology Lab, Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 200011, China.
Background And Aims:
Liver ischemia-reperfusion injury (LIRI) profoundly affects liver function and survival largely through activation of the innate immune system. In this study we sought to elucidate the underlying mechanisms by which the innate immune system impacts liver function and survival in LIRI.
Approach And Results:
RNA-seq analyses, from existing datasets of liver from mice with LIRI, was performed to identify differentially expressed genes (DEGs) associated with LIRI. Protein-protein interaction analysis revealed clusters involved in signaling pathways with a cluster anchored by Senp2, acting as a central modulator. Macrophages and monocytes were determined to be the source of Senp2 with monocyte-derived macrophages expressing the highest levels of Senp2. Experiments in a mouse model of LIRI further elucidated the expression, function, and mechanism of Senp2. Overexpression of Senp2 suppressed both the polarization of M1 macrophages and the production of inflammatory mediators. Further, Senp2-overexpressing macrophages significantly ameliorated LIRI.
Conclusions:
Our study suggests that SENP2 plays an important role in regulating LIRI by influencing macrophage polarization through the Dvl2/GSK-3β/β-catenin axis. While further validation is needed, these findings indicate that targeting SENP2-mediated pathways could be a promising approach for mitigating LIRI and enhancing therapeutic strategies.
