ArticleMolecular medicine (Cambridge, Mass.)2025
LXRα agonists ameliorates acute rejection after liver transplantation via ABCA1/MAPK and PI3K/AKT/mTOR signaling axis in macrophages.
Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Pathophysiological mechanisms of cell death affecting graft survival in liver transplantation.World journal of transplantation · 2026Review
- From network prediction to in vivo validation: luteolin attenuates cholestatic liver injury in association with PI3K/Akt/GSK-3β signalling modulation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Immunopathogenesis of antibody-mediated rejection in liver transplantation.Frontiers in immunology · 2026Review
- Multi-Component Synergy in Hepatic Trauma Repair: Network Pharmacology and Molecular Docking Decipher Panax Notoginseng's PI3K-Akt Pathway Activation.Current pharmaceutical design · 2026Article
- Leucine Attenuates Osteoarthritis via mTORC1/LXRα-Mediated Macrophage Reprogramming and Rspo2/β-Catenin Axis Suppression.Cartilage · 2025Article
- mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025Review
- Machine learning-based predictive model for the perioperative co-occurrence of T-cell-mediated rejection and pneumonia in liver transplantation.Frontiers in immunology · 2025Article
- Exploring cell death mechanisms in liver transplantation: implications for graft survival.Frontiers in immunology · 2025Review
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Authors and funding
9 authors.
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Abstract
introductionLiver X receptor α (LXRα) plays an important role in inflammatory immune response induced by hepatic ischemia-reperfusion injury (IRI) and acute rejection (AR). Macrophage M1-polarization play an important role in the occurrence and development of AR. Although the activation of LXR has anti-inflammatory effects, the role of LXRα in AR after liver transplantation (LT) has not been elucidated.
objectiveWe aimed to investigate LXRα anti-inflammatory and macrophage polarization regulation effects and mechanisms in acute rejection rat models.
methodsLXRα anti-inflammatory and liver function protective effects was initially measured in primary Kupffer cells and LT rat models. Subsequently, a flow cytometry assay was used to detect the regulation effect of LXRα in macrophage polarization. HE staining, TUNEL and ELISA were used to evaluate the co-treatment effects of TO901317 and tacrolimus on hepatic apoptosis and liver acute rejection after LT.
resultsIn this study, we found that LPS can inhibit the expression of LXRα and activate MAPK pathway and PI3K/AKT/mTOR. We also found that LXRα agonist (TO901317) could improve liver function and rat survival after LT by activating the level of ABCA1 and inhibiting MAPK. TO901317 could inhibit macrophage M1-polarization by activating PI3K/AKT/mTOR signal pathway to improve the liver lesion of AR rats after liver transplantation. Additionally, co-treatment with TO901317 and tacrolimus more effectively alleviated the damaging effects of AR following LT than either drug alone.
conclusionOur results suggest that the activation of LXRα can improve liver function and rat survival after LT by regulate ABCA1/MAPK and PI3K/AKT/mTOR signaling axis in macrophages.
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