Diabetes was an increasing public health problem nowadays. Accumulating evidences had shed a light on the involvement of endothelial cell dysfunction in the pathogenesis of diabetes-associated vascular diseases. MiR-21, a multiple-functional miRNA, was evidenced to be involved in endothelial dysfunction, however, the underlying molecular mechanisms were still unknown. In current study, we investigated the intrinsic link between miR-21 and high glucose-induced endothelial dysfunction. We demonstrated that expression of miR-21 was elevated in circulating endothelial progenitor cells from diabetes patients. Further, inhibition of miR-21 markedly enhanced high glucose-induced endothelial cytotoxicity. Furthermore, proteomic profiling was applied to analyze the downstream effectors involved in miR-21-meidated protection of endothelial cells. A total of 31 proteins were positively identified, including Annexin A2, S100A4, SOD2, Thioredoxin and DAXX. Altered expression of these proteins was validated by immunoblot. Finally, mechanistic study showed that miR-21 protected endothelial cell against high glucose-induced endothelial cytotoxicity probably by inhibiting the expression of DAXX. Our findings were considered as a significant step toward a better understanding of diabetes-associated vascular diseases.

Circular RNAs act as vital regulators in diverse diseases.However, the investigation of circular RNAs in sepsis-engendered acute kidney injury remains dismal. We aimed to explore the effects of circular RNA protein kinase C iota (circ-PRKCI) in lipopolysaccharide (LPS)-mediated HK2 cell injury. Sepsis in vitro model was established by LPS treatment. Quantitative real-time polymerase chain reaction assay was conducted for determining the levels of circ-PRKCI, microRNA-106b-5p (miR-106b-5p), and growth factor receptor binding 2-associated binding protein 1 (GAB1). Cell viability and apoptosis were evaluated using Cell Counting Kit-8 assay and flow cytometry analysis, respectively. The concentrations of interleukin-6, interleukin-1b, and tumor necrosis factor-a were measured with enzyme-linked immunosorbent assay kits. The levels of oxidative stress markers were determined using relevant commercial kits. Western blot assay was conducted for B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and GAB1 protein levels. Dualluciferase reporter assay and RNA immunoprecipitation assay were used to verify the association between miR-106b-5p and circ-PRKCI or GAB1. We found the Circ-PRKCI level was decreased in sepsis patients and LPS-induced human kidney 2 (HK-2) cells. LPS exposure inhibited cell viability and facilitated apoptosis, inflammation, and oxidative stress in HK-2 cells. Circ-PRKCI overexpression abrogated the effects of LPS on cell apoptosis, inflammation, and oxidative stress in HK-2 cells. Furthermore, circ-PRKCI was identified as the sponge for miR-106b-5p to positively regulate GAB1 expression. Overexpression of circ-PRKCI relieved LPS-mediated HK-2 cell damage by sponging miR-106b-5p. MiR-106b-5p inhibition ameliorated the injury of HK-2 cells mediated by LPS, whereas GAB1 knockdown reversed the effect. Collectively, Circ-PRKCI overex-pression attenuated LPS-induced HK-2 cell injury by regulating miR-106b-5p/GAB1 axis.