Nicotinamide mononucleotide reduced lung signals in mouse lung tissue and BEAS-2B cells, partly through /NF-kappaB-related pathways.
Evidence
This preclinical study used a mouse left-lung ischemia-reperfusion model, an in vitro BEAS-2B cold ischemia-reperfusion model, histology, inflammatory and oxidative assays, Western blotting, RT-PCR, and multi-omics profiling.
Caveat
The protective effects were shown in animal and cell models of transplantation injury, not in human lung transplant recipients or clinical outcomes.
Simplified
BACKGROUND: Lung (LIRI) is associated with a variety of postoperative complications and affects patient prognosis. β-Nicotinamide mononucleotide (NMN) has attracted much attention due to its potential role in cellular energy metabolism and antioxidant properties. Exploring the mitigating role of NMN in ischemia-reperfusion injury after lung transplantation is crucial for improving lung transplantation success and patient quality of life.
METHODS: A LIRI model was established using the mouse left lung portal clamp method, and the cold ischemia-reperfusion (CI/R) model with BEAS-2B cells in vitro was used to simulate the lung transplantation environment. The protective effect of NMN against lung ischemia-reperfusion injury was analyzed by histopathology, ELISA, immunofluorescence, Western blot and RT-PCR. Combined multi-omics profiling were used to study the mechanisms by which NMN attenuated lung ischemia-reperfusion injury.
RESULTS: NMN significantly attenuated ischemia-reperfusion-induced structural abnormalities, pulmonary edema, inflammatory infiltration and oxidative stress injury in mouse lung tissue. Similarly, NMN attenuated CI/R-induced oxidative stress and inflammatory responses in BEAS-2B cells. Based on multi-omics analysis, we found that NMN ameliorated the apoptosis after ischemia/reperfusion through down-regulation of cleaved Caspase 3, BAX and up-regulation of BCL-2. Moreover, NMN also affected mitochondrial metabolic processes, including promoting mitochondrial oxidative phosphorylation, increasing ATP synthesis, enhancing mitochondrial complex activity, decreasing ROS generation, slowing down the decrease of mitochondrial membrane potential, and inhibiting the opening of the mitochondrial membrane permeability transition pore. Mechanistically, we found that NMN attenuates inflammation and oxidative damage through activation of the and NF-κB signaling pathways, and that SIRT1-specific inhibition of EX527 reversed these protective effects of NMN against inflammation and oxidative damage in vivo and in vitro.
CONCLUSION: NMN has a protective effect on inflammation and oxidative damage induced by ischemia-reperfusion injury after lung transplantation, and the SIRT1/NF-κB pathway may be involved in one of the mechanisms of the protective effect.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07382-6.
Key numbers
6
Decrease in lung injury score
Compared to sham operation, -treated mice showed a lower lung injury score.
2.5×
Reduction in TNF-α levels
TNF-α levels decreased significantly with administration.
2.3×
Reduction in IL-6 levels
IL-6 levels were significantly lower in -treated groups.
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