<scp>UBE2C</scp> / <scp>PTTG1</scp> Regulates <scp>PANoptosis</scp> , Ferroptosis, and Autophagy to Improve Renal Ischemia–Reperfusion Injury

Ischemia-reperfusion injury (IRI) is one of the pathogenic factors of acute kidney injury (AKI). Anostosis, including apoptosis, proptosis, necroptosis, along with ferroptosis and autophagy, is involved in IRI. Based on bioinformatics analysis, we aimed to explore the effect of Ubiquitin Conjugating Enzyme E2 C/Pituitary Tumor-Transforming Gene 1 on renal IRI in the present study. The IRI model in vitro and in vivo was established; correlation of UBE2C with PTTG1, including ubiquitination through down and over-expression of UBE2C/PTTG1 construction in IRI-induced AKI was investigated. Our results indicated that IRI-induced increasing UBE2C/PTTG1 expression at 3 days reperfusion and decreased gradually at 7 days to 14 days after ischemia. Down expression of UBE2C/PTTG1 promoted apoptosis and ferroptosis while suppressing autophagy in the IRI-induced kidney. The effect of UBE2C may be reversed by intervention on PTTG1 expression, and UBE2C regulated PTTG1 expression by affecting its ubiquitination. Our results suggested that UBE2C might promote PTTG1 expression by enhancing its stability through decreasing ubiquitination to inhibit Panopolis and ferroptosis while facilitating autophagy to protect the kidney from IR-induced AKI.