Regulation of ulcerative colitis progression by ferroptosis pathway genes: HSP90AA1, SNCA, TLR4, and PTGS2

To investigate the role of the ferroptosis pathway in ulcerative colitis (UC) and conduct molecular validation.

The UC dataset GSE3365 was downloaded from the GEO database, and differentially expressed genes were identified after data correction. Ferroptosis-related genes were obtained from the FerrDb database and intersected with the differentially expressed genes. Gene ontology (GO) and KEGG enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed, leading to the identification of four hub genes. Thirty mice were randomly assigned to control, UC, and Ferrostatin-1, (Fer-1) groups (10 mice per group). UC was induced in the UC and Fer-1 groups using sodium dextran sulfate, and Fer-1, an iron death inhibitor, was injected into the Fer-1 group. Pathologic changes in colonic tissues were observed by H&E staining, serum TNF-α levels were measured with ELISA, and RT-qPCR was used to detect the expression of hub genes.

A total of 24 ferroptosis-related genes were identified in UC. GO enrichment analysis showed that these genes were involved in oxidative stress response, glucocorticoid response, and reactive oxygen species metabolism. PPI network analysis identified HSP90AA1, SNCA, TLR4, and PTGS2 as hub genes. Pathologic changes were alleviated in the Fer-1 group compared with the UC group. Serum TNF-α levels were significantly higher in the UC and Fer-1 groups than in the control group, with the UC group showing higher levels than the Fer-1 group (both P<0.05). The expression of HSP90AA1, SNCA, TLR4, and PTGS2 mRNA was significantly higher in UC and Fer-1 groups compared to the control group, with lower levels in the Fer-1 group than in the UC group (both P<0.05).

HSP90AA1, SNCA, TLR4, and PTGS2 are ferroptosis-related genes that may play a crucial role in the pathogenesis of UC by regulating the ferroptosis pathway.