ETS1 inhibition relieves renal ischemia-reperfusion injury by downregulating PARP1

To investigate the role of PARP1 inhibitors in RIR and explore the underlying mechanisms. By clamping the renal artery to induce an RIR rat model, we investigated the effects of PARP1 inhibitors and ETS proto-oncogene 1 (ETS1) on renal function and cellular DNA damage in rats using hematoxylin-eosin staining, immunofluorescence staining, ELISA, and comet assays. We constructed a RIR cell model by inducing human renal tubular epithelial HK2 cells with oxygen-glucose deprivation/reoxygenation (OGD/R). The effects of PARP1 inhibitors and ETS1 on OGD/R cell injury were investigated through CCK-8, TUNEL, immunofluorescence, ELISA, and comet assays. The binding of ETS1 and PARP1 was examined using the hTFtarget and JASPAR databases, ChIP-qPCR, dual-luciferase reporter gene assay, RT-qPCR, and western blotting. The PARP1 inhibitors Veliparib and PJ34 significantly reduced kidney damage and promoted the recovery of renal function in rats with RIR. Pretreatment with Veliparib and PJ34 enhanced the proliferation of HK2 cells treated with OGD/R, reduced cell apoptosis, and decreased DNA damage. ETS1, as a transcription factor, regulates the promoter of PARP1 and positively regulates PARP1 expression. Knockdown of ETS1 inhibited PARP1 transcription, reduced HK2 cell apoptosis, decreased DNA damage, and diminished inflammatory cytokines and kidney injury in RIR rats. ETS1 knockdown exerts a protective effect on the kidneys of rats with ischemia-reperfusion injury by inhibiting PARP1 transcription.