Revealing the toxicity mechanisms and potential targets of PM2.5-induced different types of cystitis based on Mendelian randomization and network toxicology

The current study explored the potential toxic mechanisms and targets of PM_2.5-induced different types of cystitis by using Mendelian randomization (MR) analysis and network toxicology. We first found a significant causal association between PM_2.5 and cystitis by MR analysis. Subsequently, we obtained a total of 18,763 PM_2.5-regulated genes through the CTD database, and the enrichment analysis suggested that PM_2.5 is mainly closely related to biological functions such as oxidative stress, apoptosis, cytokine production, and inflammation. Next, we obtained disease targets for total cystitis and four common types of cystitis (interstitial cystitis, hemorrhagic cystitis, radiation cystitis, and bacterial cystitis) through the GeneCards database, and intersected them with PM_2.5-regulated genes, and the intersected genes we defined as PM_2.5-regulated genes in the corresponding types of cystitis. Enrichment analysis suggested that PM_2.5 was strongly associated with cytokine production, inflammatory response, and oxidative stress in different types of cystitis. Subsequently, we constructed PPI protein networks in each of the different types of cystitis, and utilized different algorithms in Cytoscape software to identify the key regulatory genes. Among them, we found that IL1B and CD4 were associated with all types of cystitis, and therefore, we defined them as Hub genes in cystitis. In summary, our findings provide a theoretical basis for understanding the potential toxic mechanisms and targets of PM_2.5-induced cystitis.