Inhibition of Ferroptosis in Prostatitis Model by Low Intensity Extracorporeal Shock Wave Therapy through the Integrin-β1/NRF2 Axis

PURPOSE: Although low-intensity extracorporeal shock wave therapy (Li-ESWT) is used clinically for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), its mechanisms remain inadequately understood. This study aimed to explore Li-ESWT-mediated mechanotransduction signaling and its association with ferroptosis in CP/CPPS models. MATERIALS AND METHODS: siRNA or overexpression plasmid, with Ferrostatin-1 used as a reference control. The changes in NRF2-xCT/GPX4 expression, ferrous iron, and lipid peroxidation were evaluated to clarify the mechanisms by which Li-ESWT regulates ferroptosis. RESULTS: , Integrin-β1 knockdown reduced NRF2, xCT, and GPX4 expression, abolishing the protective effects of Li-ESWT against LPS-induced ferroptosis, as evidenced by increased lipid peroxidation and ferrous iron accumulation. Similarly, NRF2 knockdown negated the anti-ferroptotic effect of Li-ESWT, whereas ectopic overexpression of xCT/GPX4 restored ferroptosis suppression. CONCLUSIONS: activating the Integrin-β1/NRF2 pathway.