NOD-like receptors mediate inflammatory lung injury during plateau hypoxia exposure

The lung is an important target organ for hypoxia treatment, and hypoxia can induce several diseases in the body.

Our study suggested that the NF-κBp65 and p38 MAPK signaling pathways may be activated in the lungs of rats during plateau hypoxia. Upregulated expression of NF-κBp65 and p38 MAPK can promote the transcription of downstream inflammatory factors, thereby aggravating the occurrence and development of lung tissue remodeling.

We performed transcriptome sequencing for the lungs of rats exposed to plateau hypoxia at 0 day and 28 days. Sequencing libraries were constructed, and enrichment analysis of the differentially expressed genes (DEGs) was implemented using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, experimental validation was executed by quantitative real-time PCR (qRT-PCR) and western blot.

The results showed that the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway that was involved in immunity may play a crucial function in lung injury caused by plateau hypoxia. And the expressions of NOD1, NOD2, IL-1β, TNF-α, IL-6, and IL-18 were higher at 28 days of exposure to plateau hypoxia than that at 0 day. Similarly, CARD9, MYD88, p38 MAPK, and NF-κB p65, which are related to the NF-κB and MAPK signaling pathways, also demonstrated increased expression at 28 days exposure to plateau hypoxia than at 0 day. Conclusions: Our study suggested that the NF-κBp65 and p38 MAPK signaling pathways may be activated in the lungs of rats during plateau hypoxia. Upregulated expression of NF-κBp65 and p38 MAPK can promote the transcription of downstream inflammatory factors, thereby aggravating the occurrence and development of lung tissue remodeling.