Human KPNA4 blocking peptide

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.

Proper regulation of the coordinated transcriptional program that drives oligodendrocyte (OL) differentiation is essential for central nervous system myelin formation and repair. Nuclear import, mediated in part by a group of karyopherin alpha (Kpna) proteins, regulates transcription factor access to the genome. Understanding how canonical nuclear import functions to control genomic access in OL differentiation may aid in the creation of novel therapeutics to stimulate myelination and remyelination. Here, we show that members of the Kpna family regulate OL differentiation, and may play distinct roles downstream of different pro-myelinating stimuli. Multiple family members are expressed in OLs, and their pharmacologic inactivation dose-dependently decreases the rate of differentiation. Additionally, upon differentiation, the three major Kpna subtypes (P/alpha 2, Q/alpha 3, S/alpha 1) display differential responses to the pro-myelinating cues T3 and CNTF. Most notably, the Q/a3 karyopherin Kpna4 is strongly upregulated by CNTF treatment both compared with T3 treatment and other Kpna responses. Kpna4 inactivation results in inhibition of CNTF-induced OL differentiation, in the absence of changes in proliferation or viability. Collectively, these findings suggest that canonical nuclear import is an integral component of OL differentiation, and that specific Kpnas may serve vital and distinct functions downstream of different pro-myelinating cues.