Circ_0068087 knockdown attenuates high‐glucose‐induced human tubular epithelial cell injury in a microribonucleic acid/progestin and adipoQ receptor 3‐dependent manner in diabetic nephropathy

Abstract

Abstract Aims/Introduction Previous studies have shown that circular ribonucleic acid mediates the occurrence of diabetic nephropathy. This study aimed to analyze the effects of circ_0068087 on high‐glucose (HG)‐induced human kidney 2 (HK2) cell dysfunction. Materials and Methods Circ_0068087, miR‐580‐3p, and progestin and adipoQ receptor 3 (PAQR3) expression were detected by quantitative reverse transcription polymerase chain reaction. Cell viability and proliferation were investigated by Cell Counting Kit‐8 and EdU assays, respectively. The cell apoptotic rate was assessed by flow cytometry. Inflammatory response was assessed by enzyme‐linked immunoassays. Oxidative stress was evaluated by a superoxide dismutase activity assay kit and lipid peroxidation malondialdehyde assay kit. Molecular interaction was identified by dual‐luciferase reporter assay. Results Circ_0068087 and PAQR3 expression were significantly upregulated in diabetic nephropathy patients. HG treatment inhibited HK2 cell proliferation, but induced cell apoptosis, inflammation, oxidative stress and epithelial–mesenchymal transition by regulating circ_0068087. Circ_0068087 acted as a microribonucleic acid‐580‐3p (miR‐580‐3p) sponge, and miR‐580‐3p targeted PAQR3. Furthermore, circ_0068087 depletion repressed PAQR3 expression through miR‐580‐3p. MiR‐580‐3p inhibitors or PAQR3 introduction attenuated circ_0068087 silencing mediated‐effects in HG‐treated HK2 cells. Conclusion Circ_0068087 promoted HG‐induced HK2 cell injuries by the regulation of the miR‐580‐3p/PAQR3 pathway.

Keywords

• Circ_0068087
• Diabetic nephropathy
• Progestin and adipoQ receptor 3