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Updated: Apr 17, 2026
Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Downregulated PLAU alleviates acute rejection after liver transplantation by targeting Ptgs2 in macrophages
Qiong Qin1, Zhe-Chao Wang1,2, Shi-Ming Jiang1
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background:
Acute rejection (AR) is a major determinant of poor prognosis after liver transplantation (LT), and macrophage M1-polarization can induce AR. Urokinase-type plasminogen activator (PLAU) has been implicated in the regulation of several liver diseases, but its role in AR remains unclear.
Methods:
In this study, through bioinformatics analysis and transcriptome sequencing, we find that PLAU and prostaglandin-endoperoxide synthase 2 (Ptgs2) can regulate macrophage polarization. To elucidate the effects of PLAU and Ptgs2 on AR, dynamic changes in PLAU and Ptgs2 expression are detected in both peripheral blood mononuclear cells (PBMCs) from clinical LT patients and hepatic macrophages from LT rats. Subsequently, to investigate the specific regulatory roles in macrophage M1-polarization and AR, downregulating PLAU and Ptgs2 rescue experiments are conducted in vivo and in vitro. Finally, potential signaling pathways are further identified through KEGG enrichment analysis.
Results:
The expression of PLAU and Ptgs2 is increased in PBMCs from LT patients and in macrophages from LT rats, and most significantly on postoperative day 7. Downregulating PLAU alleviates AR and suppresses M1-polarization of macrophages. However, Ptgs2 rescue exacerbates AR and promotes M1-polarization of macrophages. The potential mechanism involves regulating the Protein kinase B/Nuclear factor kappa B (AKT/NF-κB) pathway.
Conclusion:
In summary, downregulated the PLAU/Ptgs2 axis can attenuate AR by regulating macrophage polarization, offering a promising new therapeutic target for preventing and treating AR.
Insights
Downregulating the PLAU/Ptgs2 axis can attenuate acute rejection after liver transplantation by regulating macrophage polarization. This offers a promising new therapeutic target for preventing and treating acute rejection.
Area of Science:
- Immunology
- Transplantation Biology
- Molecular Medicine
Background:
- Acute rejection (AR) significantly impacts liver transplant (LT) outcomes.
- Macrophage M1-polarization is a key driver of AR.
- The role of urokinase-type plasminogen activator (PLAU) in LT-associated AR is not well understood.
Purpose of the Study:
- To investigate the roles of PLAU and prostaglandin-endoperoxide synthase 2 (Ptgs2) in macrophage polarization and AR after LT.
- To identify potential therapeutic targets for mitigating AR.
Main Methods:
- Bioinformatics analysis and transcriptome sequencing.
- Detection of PLAU and Ptgs2 expression in clinical LT patients and LT rat models.
- In vivo and in vitro rescue experiments involving PLAU and Ptgs2 downregulation.
- KEGG pathway enrichment analysis.
Main Results:
- PLAU and Ptgs2 expression increased in LT patients and rats, peaking on postoperative day 7.
- Downregulating PLAU alleviated AR and suppressed M1 macrophage polarization.
- Ptgs2 upregulation exacerbated AR and promoted M1 macrophage polarization.
- The AKT/NF-κB pathway was implicated in the observed effects.
Conclusions:
- The PLAU/Ptgs2 axis plays a critical role in regulating macrophage polarization and AR post-LT.
- Targeting the PLAU/Ptgs2 axis offers a potential therapeutic strategy for preventing and treating AR.
- Understanding the molecular mechanisms, including the AKT/NF-κB pathway, is crucial for developing effective interventions.
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