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Updated: Sep 8, 2025
Author Spotlight: Insights into the Effect of Ischemia Reperfusion on Lung Transplantation
Published on: April 12, 2024
MMP2 and MMP9 contribute to lung ischemia-reperfusion injury via promoting pyroptosis in mice
Peng Zhou1, Nai-Cheng Song2, Zhi-Kun Zheng3
1Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background:
Lung ischemia-reperfusion injury (LIRI) is a cause of poor prognosis in several lung diseases and after lung transplantation. In LIRI, matrix metalloproteinases and pyroptosis indicators change in parallel, both of them involvement of inflammatory modulation, but it is unclear whether they are related to each other.
Methods:
We analyzed the matrix metalloproteinases (MMPs) changes from RNA sequencing (RNA-Seq) data of human transplantation and rat ischemia-reperfusion lung tissues in the Group on Earth Observations (GEO) database. Then established the mouse LIRI model to validate the changes. Further, the severity of lung injury was measured after intervening the matrix metalloproteinases changes with their selective inhibitor during Lung ischemia-reperfusion. Meanwhile, lung, pyroptosis was assessed by assaying the activity of Caspase-1 and interleukin 1β (IL-1β) before and after intervening the matrix metalloproteinases changes.
Results:
The RNA-Seq data revealed that matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9) mRNA expression was elevated both in human lung transplantation and rat lung ischemia-reperfusion tissues, consistent with the change in our mouse model. At the same time, the activity of Caspase-1 and IL-1β were increased after LIRI. While, the lung injury was attenuated for the use of MMP2 and MMP9 selective inhibitor SB-3CT. Likewise, lung pyroptosis alleviated when treatment the mice with SB-3CT in LIRI.
Conclusion:
We conclude that MMP2 and MMP9 are involved in the process of LIRI, the mechanism of which is related to the promotion of lung pyroptosis.
Insights
Matrix metallopeptidase 2 (MMP2) and MMP9 promote lung ischemia-reperfusion injury (LIRI) by enhancing pyroptosis. Inhibiting MMP2 and MMP9 alleviates lung injury and pyroptosis in LIRI models.
Area of Science:
- Cardiovascular Sciences
- Immunology
- Pulmonology
Background:
- Lung ischemia-reperfusion injury (LIRI) is a significant factor in poor outcomes for lung diseases and transplantation.
- Matrix metalloproteinases (MMPs) and pyroptosis indicators are altered in parallel during LIRI, suggesting a potential link.
- The precise relationship between MMPs and pyroptosis in LIRI remains unclear.
Purpose of the Study:
- To investigate the role of matrix metalloproteinases (MMPs) in lung ischemia-reperfusion injury (LIRI).
- To determine if MMPs are associated with pyroptosis during LIRI.
- To evaluate the therapeutic potential of MMP inhibition in LIRI.
Main Methods:
- Analyzed MMP expression using RNA sequencing data from human and rat lung tissues.
- Established a mouse model of LIRI to validate findings.
- Assessed lung injury, pyroptosis markers (Caspase-1, IL-1β), and therapeutic effects of MMP inhibitors (SB-3CT).
Main Results:
- Elevated mRNA expression of MMP2 and MMP9 was observed in human and rat LIRI tissues and validated in the mouse model.
- Increased activity of Caspase-1 and IL-1β indicated heightened pyroptosis post-LIRI.
- Selective inhibition of MMP2 and MMP9 with SB-3CT attenuated lung injury and reduced pyroptosis.
Conclusions:
- MMP2 and MMP9 play a crucial role in the pathogenesis of LIRI.
- The mechanism involves the promotion of lung pyroptosis by MMP2 and MMP9.
- Targeting MMP2 and MMP9 presents a potential therapeutic strategy for LIRI.
