Key result
Preclinical models identify upregulated PTGS2, CCL2, and RELB as potential biomarkers for lung ischemia-reperfusion injury.
Why the study?
Ischemia-reperfusion injury is a significant complication after lung transplantation that contributes to poor prognosis, but its molecular targets and mechanisms are not fully understood.
PTGS2, CCL2, and RELB are potential biomarkers and therapeutic targets for lung ischemia-reperfusion injury, associated with increased immune cell infiltration.
Requires human validation before clinical use; leaves open therapeutic targeting in lung IRI.
BACKGROUND: Ischemia-reperfusion injury (IRI) is a significant complication that can occur following lung transplantation and is known to contribute to poor prognosis. Our research aimed to investigate the potential molecular targets and mechanisms involved in lung IRI (LIRI), in order to improve our understanding of this condition. METHOD: We downloaded gene expression datasets (GSE127003 and GSE18995) linked to LIRI from the GEO database. Using WGCNA, we identified LIRI-related modules. Functional enrichment analyses were performed on the modules showing significant correlation with LIRI. Core immune-related genes (IRGs) were identified and validated using the GSE18995 dataset. A rat LIRI model was established to validate the expression changes of core IRGs. The LIRI groups were subjected to 60 min of warm ischemia followed by 120 min of reperfusion. Additionally, the xCell algorithm was used to characterize the immune landscape and analyze the relationships between hub IRGs and infiltrating immune cells. RESULTS: A total of 483 genes from the turquoise module were identified through WGCNA, with a predominant enrichment in immune- and inflammation-related pathways. Three IRGs (PTGS2, CCL2, and RELB) were found to be up-regulated after reperfusion in both GSE127003 and GSE18995 datasets, and this was further confirmed using the rat LIRI model. The xCell analysis revealed that immune score, CD8+ naive T cells, eosinophils, neutrophils, NK cells, and Tregs were upregulated after reperfusion. PTGS2, CCL2, and RELB showed positive correlations with CD8+ naive T cells, monocytes, neutrophils, and Tregs. CONCLUSION: PTGS2, CCL2, and RELB were found to be potential biomarkers for LIRI. Immune and microenvironment scores were higher after reperfusion compared to before reperfusion. PTGS2, CCL2, and RELB appear to play a crucial role in the development of LIRI and may contribute to it by increasing the number of immune cells. Our findings offer new perspectives on potential treatment targets and the pathogenesis of LIRI.
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Qian et al. (2023) studied Lung ischemia-reperfusion injury. Lung ischemia-reperfusion injury vs. Before reperfusion was evaluated on Identification of core immune-related genes and immune infiltration changes. Bioinformatics analysis and a rat model identified PTGS2, CCL2, and RELB as upregulated immune-related genes and potential biomarkers for lung ischemia-reperfusion injury.
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