KPNA4 blocking peptide

Interferon (IFN)-mediated antiviral response is an important part of host defense. Previous studies reported that porcine circovirus type 2 (PCV2) inhibits interferon production, but the mechanism is still poorly understood. In this study, PCV2 suppresses IFN-beta and IRF3 promoters and mRNA level of IFN-beta induced by ISD or Poly(I:C), but has no effect on the activation of AP-1 and NF-kB. Furthermore, PCV2 decreases the mRNA level of IFN-beta and IFN-beta promoter activity driven by STING, TBK1, IRF3, and IRF3/5D, and causes a reduction in the protein level of nuclear p-IRF3. In addition, PCV2 interrupts the interaction of KPNA3, rather than KPNA4, with p-IRF3. Overexpression of KPNA3 restores IFN-beta promoter activity. These results indicate that PCV2 disrupts the interaction of KPNA3 with p-IRF3 and blocks p-IRF3 translocation to the nucleus, thereby inhibiting IFN-beta induction in PK-15 cells.

The aim of the present study was to measure the level of microRNA (miRNA or miR)-24 in the serum of patients with atherosclerosis and to investigate the effect of miR-24 on the expression of importin-alpha 3 and tumor necrosis factor (TNF)-alpha, as well as the proliferation and migration of vascular endothelial cells. A total of 30 patients with atherosclerosis admitted to hospital between January and June 2016 were enrolled in the present study; 30 healthy subjects with a similar age range were enrolled as controls. Peripheral blood (10 ml) was collected from all participants. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-24 mimic using Lipofectamine 2000. TargetScan was used to elucidate whether importin-alpha 3 (KPNA4) was a target gene of miR-24. Expression levels of miR-24 and mRNAs were measured using reverse transcription-quantitative polymerase chain reaction, and protein expression was determined using western blotting. Cell Counting Kit 8 assay was used to assess the proliferation of HUVECs, and a Transwell assay was performed to detect the migration of HUVECs. Expression of miR-24 in peripheral blood from patients with atherosclerosis was significantly lower when compared with healthy subjects (P<0.05). Overexpression of miR-24 was demonstrated to significantly inhibit the transcription and translation of the importin-alpha 3 gene (P<0.05) and negatively regulate the expression of endothelial inflammatory factor TNF-alpha (P< 0.05). Furthermore, overexpression of miR-24 significantly inhibited the proliferation and migration of HUVECs (P<0.05), and miR-24 knockdown significantly promoted these processes (P<0.05). The results of the present study suggest that miR-24 exerts its effect in atherosclerosis by blocking the nuclear factor-kappa B signaling pathway, regulating inflammation in endothelial cells, and inhibiting the proliferation and migration of vascular endothelial cells.