CircRNA-DAPK1 promotes vascular cell pyroptosis in diabetes by regulating the circ-DAPK1/miR-4454/TXNIP axis.

Abstract

Background Circular RNAs have been demonstrated to play an important role in the development of vascular diseases. However, little is known about the role of circ-021774, also named circ-DAPK1, in vascular cell pyroptosis. Methods Circ-DAPK1 was selected from circular RNA sequencing data of HUVECs treated with high glucose medium and normal medium. RT-qPCR was used to determine the expression of circ-DAPK1 in vivo and in vitro. Dual luciferase reporter assay, fluorescence in situ hybridization (FISH) and RNA immunoprecipitation (RIP) were performed to prove the interaction of circ-DAPK1, miRNA-4454 and thioredoxin-interactingprotein (TXNIP). Adeno-associated virus (AAV) was injected intravenously to establish mouse models. PI staining, western-blot and transmission electron microscopy (TEM) analyses were performed to identify the role of circ-DAPK1 in promoting pyroptosis. Results We found that circ-DAPK1 was highly expressed in high glucose medium cultured HUVECs and db/db mice. In vitro and in vivo experiments demonstrated that circ-DAPK1 knockdown decreased the number of PI+ cells, the expression of ASC, NLRP3, GSDMD-N, cleaved caspase-1, IL-18 and IL-1β. In a mechanistic study, the circ-DAPK1/miRNA-4454/TXNIP signaling axis was demonstrated to promote vascular cell pyroptosis in diabetes. Conclusions Circ-DAPK1 functions as a promoter of vascular cell pyroptosis in diabetes via the circ-DAPK1/miRNA-4454/TXNIP signaling axis.