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PTX3 exacerbates hepatocyte pyroptosis in hepatic ischemia-reperfusion injury by promoting macrophage M1 polarization
Peng Jiang1, Lijian Luo2, Xinqiang Li1
1Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Backgrounds:
Hepatic ischemia-reperfusion injury (IRI) triggers macrophage activation, which in turn mediates inflammatory responses and affects tissue repair and injury severity. Pentraxin 3 (PTX3) is vital in immune regulation and inflammatory processes. In this study, we aim to investigate the potential role of PTX3 in macrophage-mediated hepatic IRI.
Methods:
Gene expression profiles and single-cell data were obtained from the Gene Expression Omnibus (GEO) database. Immunohistochemistry was used to evaluate the expression levels of PTX3, CD68, and CD86 in samples from the human and mouse hepatic IRI models. The effects of PTX3 knockdown or overexpression on macrophage polarization were assessed in Raw264.7. PTX3 knockdown/ overexpression in Raw264.7 and co-culturing with AML12 were performed under conditions of hypoxia-reoxygenation (H/R) to examine pyroptosis and injury in AML12.
Results:
PTX3 expression was significantly upregulated in both human and mouse hepatic IRI model samples. Bulk and single-cell RNA-seq data analyses revealed that PTX3 is associated with inflammatory response pathways and macrophage activation. Macrophages with high PTX3 expression exhibit M1-like characteristics. Similarly, overexpression of PTX3 promotes M1 polarization of Raw264.7 after H/R, while the knockdown group exhibits reduced M1 polarization. Co-culture results indicated that pyroptosis in AML12 was significantly reduced after H/R in the PTX3 knockdown group, whereas the PTX3 overexpression group exhibited the opposite outcome.
Conclusion:
PTX3 regulates macrophage polarization during hepatic IRI, consequently influencing hepatocellular pyroptosis.
Insights
Pentraxin 3 (PTX3) regulates macrophage polarization in liver injury, impacting inflammatory responses and cell death. This study reveals PTX3
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Background:
- Hepatic ischemia-reperfusion injury (IRI) involves macrophage activation, mediating inflammation and tissue repair.
- Pentraxin 3 (PTX3) plays a key role in immune regulation and inflammation.
Purpose of the Study:
- Investigate the role of PTX3 in macrophage-mediated hepatic IRI.
- Determine PTX3's influence on macrophage polarization and hepatocellular pyroptosis.
Main Methods:
- Analyzed Gene Expression Omnibus (GEO) data for gene expression and single-cell profiles.
- Utilized immunohistochemistry to assess PTX3, CD68, and CD86 expression in hepatic IRI models.
- Examined PTX3 knockdown/overexpression effects on macrophage polarization (Raw264.7) and pyroptosis (AML12) under hypoxia-reoxygenation (H/R).
Main Results:
- PTX3 expression was significantly upregulated in human and mouse hepatic IRI samples.
- PTX3 expression correlated with inflammatory pathways and macrophage activation, particularly M1-like polarization.
- PTX3 modulation altered macrophage polarization and significantly affected H/R-induced pyroptosis in hepatocytes.
Conclusions:
- PTX3 is a key regulator of macrophage polarization in hepatic IRI.
- PTX3 influences hepatocellular pyroptosis, highlighting its therapeutic potential in liver injury.
