Resveratrol Inhibits circ_0074371-related Pathway to Alleviate Sepsis-induced Acute Kidney Injury

Abstract

Resveratrol has a protective effect on sepsis-induced acute kidney injury (AKI). Circ_0074371 has been confirmed to inhibit sepsis-induced AKI process, but whether resveratrol inhibits sepsis-induced AKI by regulating circ_0074371-related pathway remains unclear. In this study, lipopolysaccharide (LPS)-induced renal tubular epithelial cells (HK2) were used to mimic AKI cell models. Quantitative real-time PCR was used to detect relative expression of circ_0074371, microRNA (miR)-145-5p and inositol polyphosphate multikinase (IPMK). Cell proliferation and apoptosis were detected by cell counting kit 8 assay, EdU assay and flow cytometry. The levels of inflammation factors were measured by ELISA assay, and MDA level and SOD activity were examined to assess oxidative stress. Protein expression of IPMK was evaluated by western bolt analysis. The relationship between miR-145-5p and circ_0074371 or IPMK was confirmed by dual-luciferase reporter assay. It was showed that circ_0074371 was upregulated in AKI patients and LPS-induced HK2 cells, and silencing of circ_0074371 promoted proliferation and inhibited apoptosis, inflammation and oxidative stress in LPS-induced HK2 cells. In terms of mechanism, circ_0074371 sponged miR-145-5p to positively regulate IPMK. IPMK overexpression could reverse the relieving effect of circ_0074371 knockdown on LPS-induced HK2 cell injury. Moreover, resveratrol suppressed LPS-induced apoptosis, inflammation and oxidative stress in HK2 cells, and circ_0074371 overexpression also reversed the protective effect of resveratrol against LPS-induced cell injury. Our data suggested that resveratrol alleviated LPS-induced HK2 cell injury by inactivating the circ_0074371/miR-145-5p/IPMK axis.

Keywords: Acute kidney injury; Circ_0074371; LPS; Resveratrol; Sepsis.