Mechanistic Insights Into hsa_circ_0005654-Induced Ferroptosis in Diabetic Foot Ulcers Through IGF2BP2 Interaction

This study investigated the molecular mechanism by which hsa_circ_0005654 aggravates diabetic foot ulcers (DFUs) by promoting ferroptosis. A DFU rat model was established, and lentiviral vectors interfering with circ_0005654 and IGF2BP2 expression were injected into DFU rats by tail vein. The successful injection of lentiviral vectors was verified by RT-qPCR. The histopathology of foot ulcer tissues of DFU rats was observed by HE staining. Iron deposition was observed by Perls' Blue staining. Inflammatory factors were detected by ELISA. Protein expression of ferroptosis markers (GPX4 and SLC7A11) was measured by Western blot. The interaction of circ_0005654 with IGF2BP2 was verified by RNA pull-down assay and RIP assay. Iron deposition and inflammatory factor levels were increased in foot ulcer tissues of DFU rats, and wound healing was impaired. Liproxstatin-1, a ferroptosis inhibitor, promoted wound healing in DFU rats by inhibiting ferroptosis and inflammation. circ_0005654 expression was up-regulated. Down-regulating circ_0005654 promoted wound healing in DFU rats by inhibiting ferroptosis and inflammation. circ_0005654 could interact with IGF2BP2, and up-regulating IGF2BP2 attenuated the effects of circ_0005654 down-regulation in DFU rats. circ_0005654 promotes ferroptosis to aggravate DFU by interacting with IGF2BP2.