Integrated Analysis of Metabolomics and Proteomics Reveals the Potential Mechanism of Lung Injury Induced by Di(2‐Ethylhexyl) Phthalate

Di(2-ethylhexyl) phthalate (DEHP) has been widely detected in environmental compartments and is highly carcinogenic to humans, but the toxic effects of DEHP on lung injury and its mechanisms are still not clear. Herein, the effects of lung injury were evaluated both in vivo and in vitro; meanwhile, the metabolomics and proteomics methodologies were employed to elucidate the intracellular mechanisms of BEAS-2B cells. The results showed that MEHP treatment significantly decreased cell viability and caused inflammation and fibrosis changes in vivo and in vitro, manifested as abnormal expression of associated genes. There were 26 upregulated and 8 downregulated metabolites found in BEAS-2B cells exposed to MEHP, which mainly focused on fatty acid metabolism pathways. In addition, the tricarboxylic acid (TCA) cycle, alanine, aspartate, and glutamate metabolism, purine metabolism, butanoate metabolism, and ribosome synthesis are also important events in DEHP pathophysiology. Furthermore, proteomics methodologies and correlation analysis show that PLIN2 and HMGCS1 may be involved in the fatty acid synthesis pathway. These results expand the existing understanding of the molecular basis of DEHP-induced lung injury and progression, offering a new perspective for exploring its pathological mechanisms.