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

Aims/IntroductionPrevious 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 MethodsCirc_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.ResultsCirc_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.ConclusionCirc_0068087 promoted HG-induced HK2 cell injuries by the regulation of the miR-580-3p/PAQR3 pathway. This work showed circ_0068087 depletion ameliorated high-glucose-induced HK2 cell apoptosis, inflammation and oxidative stress by targeting the microribonucleic acid-580-3p/progestin and adipoQ receptor 3 pathway in vitro, suggesting that the blockade of the circ_0068087/microribonucleic acid-580-3p/progestin and adipoQ receptor 3pathway might be a therapeutic approach for diabetic nephropathy. However, the detailed mechanism of progestin and adipoQ receptor 3 modulating HG-induced HK2 cell disorders remains to be elucidated. In addition, mouse model experiments and clinical trials should be carried out to validate the present conclusion.dagger image