Study on pyroptosis-related genes Casp8, Gsdmd and Trem2 in mice with cerebral infarction.

OBJECTIVE

Cerebral infarction is the main cause of death in patients with cerebrovascular diseases. Our research aimed to screen and validate pyroptosis-related genes in cerebral infarction for the targeted therapy of cerebral infarction.

METHODS AND RESULTS

A total of 1,517 differentially expressed genes (DEGs) were obtained by DESeq2 software analysis. Gene set enrichment analysis results indicated that genes of middle cerebral artery occlusion (MCAO) mice aged 3 months and 18 months were enriched in pyroptosis, respectively. Differentially expressed pyroptosis-related genes (including Aim2, Casp8, Gsdmd, Naip2, Naip5, Naip6 and Trem2) were obtained through intersection of DEGs and genes from pyroptosis Gene Ontology Term (GO:0070269), and they were up-regulated in the brain tissues of MCAO mice in GSE137482. In addition, Casp8, Gsdmd, and Trem2 were verified to be significantly up-regulated in MCAO mice in GSE93376. The evaluation of neurologic function and triphenyltetrazolium chloride staining showed that the MCAO mouse models were successfully constructed. Meanwhile, the expressions of TNF-, pyroptosis-related proteins, Casp8, Gsdmd and Trem2 in MCAO mice were significantly up-regulated. We selected Trem2 for subsequent functional analysis. OGD treatment of BV2 cell significantly upregulated the expressions of Trem2. Subsequent downregulation of Trem2 expression in OGD-BV2 cells further increased the level of pyroptosis. Therefore, Trem2 is a protective factor regulating pyroptosis, thus influencing the progression of cerebral infarction.

CONCLUSIONS

Casp8, Gsdmd and Trem2 can regulate pyroptosis, thus affecting cerebral infarction.