Bioinformatics analysis and experimental validation reveal that heat HSP90AA1 enhances intestinal ischemia...

Intestinal ischemia/reperfusion (I/R) injury is a serious threat to human health and has high mortality and morbidity rates. Several studies have examined the role of necroptosis in intestinal I/R injury. However, the specific mechanism and signaling pathways involved in necroptosis in intestinal I/R are still unclear. Bioinformatics analysis and experimental validation were utilized to investigate the role of necroptosis in intestinal I/R injury. The dataset of target genes and disease genes was constructed using the R programming language and software environment. An interaction network of genes or proteins was built using GO and KEGG enrichment analysis to investigate the likely mechanism involved. Finally, the potential role of necroptosis in intestinal I/R injury was further verified experimentally. Eighteen differentially expressed genes were identified via the construction of target and disease gene dataset. The core gene heat shock protein 90 alpha family class A member 1 (HSP90AA1) was identified via coexpression network analysis of related protein and genes. The expression of HSP90AA1 and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) in human ischemic intestinal tissues were increased in ischemic intestinal tissue (P < 0.05). The same results were also shown in IEC-6 cells subjected to H/R injury, where the expression of HSP90AA1 and p-MLKL was considerably greater in the H/R group than in the normal group (P < 0.05). We further used siRNA to inhibit HSP90AA1 expression in IEC-6 cells, the p-MLKL protein expression level was lower in the H/R + si-HSP90AA1 group than in the H/R group (P < 0.05). HSP90AA1 promotes the development of intestinal I/R-induced necroptosis and plays a crucial role in intestinal I/R injury. HSP90AA1 may be a new therapeutic target for intestinal I/R injury.