Mechanism of simulated lunar dust-induced lung injury in rats based on transcriptomics

Abstract Lunar dust particles are an environmental threat to lunar astronauts, and inhalation of lunar dust can cause lung damage. The current study explored the mechanism of lunar dust simulant (CLDS-i) inducing inflammatory pulmonary injury. Wistar rats were exposed to CLDS-i for 4 h/d and 7d/week for 4 weeks. Pathological results showed that a large number of inflammatory cells gathered and infiltrated in the lung tissues of the simulated lunar dust group, and the alveolar structures were destroyed. Transcriptome analysis confirmed that CLDS-i was mainly involved in the regulation of activation and differentiation of immune inflammatory cells, activated signaling pathways related to inflammatory diseases, and promoted the occurrence and development of inflammatory injury in the lung. Combined with metabolomics analysis, the results of joint analysis of omics were found that the genes Kmo, Kynu, Nos3, Arg1 and Adh7 were involved in the regulation of amino acid metabolism in rat lung tissues, and these genes might be the key targets for the treatment of amino acid metabolic diseases. In addition, the imbalance of amino acid metabolism might be related to the activation of nuclear factor kappaB (NF-κB) signaling pathway. The results of quantitative real-time polymerase chain reaction and Western blot further confirmed that CLDS-i may promote the occurrence and development of lung inflammation and lead to abnormal amino acid metabolism by activating the B cell activation factor (BAFF)/ B cell activation factor receptor (BAFFR)-mediated NF-κB signaling pathway.