Inhibition of the NF-κB signaling pathway on endothelial cell function and angiogenesis in mice with acute cerebral infarction

Abstract

This study was aimed to investigate whether interferon (IFN)-induced protein 35 (IFI35) affects the signaling pathway of nuclear factor-kappa B (NF-κB) and to observe the effect of different expressions of IFI35 on the proliferation of endothelial cells and angiogenesis in rats with acute cerebral infarction. A suture method was adopted to prepare a mouse model of permanent middle cerebral artery occlusion (PMCAO). After the treatment of cerebral artery occlusion in 200 healthy male mice (weighting 20g-40g), 47 mice were selected and the double luciferase assay was used to identify different structural domains of IFI35; for the remaining 153 mice, RT-PCR and immunohistochemical assays were used to detect the mRNA expression of glioma-associated oncogene homolog 1 (Gli1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and CD105 (endoglin). The results showed that IFI35 could reduce the level of p65 protein (REL-A) in the nucleus while affecting the production of p-p65 in the cytoplasm. At the same time, IFI35 could be used in combination with a NID1 protein domain + Nmi protein to inhibit the signaling pathway of NF-κB. Expressions of Gli1, VEGF, bFGF, and CD105 in the IFI35 treatment group were all significantly reduced (P less than0.05). In conclusion, IFI35 could suppress the activation of the NF-κB signaling pathway, reduce the proliferating potential of vascular endothelial cells, and lower the expression of vascular growth factors, thereby inhibiting angiogenesis in mice with acute cerebral infarction.