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Updated: Jun 29, 2026
Shock Wave Application to Cell Cultures
Published on: April 8, 2014
Inhibition of Ferroptosis in Prostatitis Model by Low Intensity Extracorporeal Shock Wave Therapy through the
Dongxu Lin1, Kang Li1, Wenbo Kuang1
1Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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:
Experimental autoimmune prostatitis (EAP) was induced by intradermal prostate antigen immunization. Rats received Li-ESWT, with additional groups treated with the ferroptosis inducer RAS-selective lethal 3 (RSL3) or iron chelator deferoxamine (DFO). The rats were analyzed histologically and biochemically to assess immune responses, fibrosis, oxidative stress, ferroptosis markers, and related signaling. In vitro, Li-ESWT was applied to lipopolysaccharide (LPS)-stimulated RWPE-1 cells. The Integrin-β1-NRF2-xCT/GPX4 axis was modulated via 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:
EAP rats recapitulated key pathological features of CP/CPPS, which were alleviated by Li-ESWT. Specifically, Li-ESWT reduced the inflammatory response by inhibiting CD3⁺ T cells and CD68⁺ macrophages infiltration, suppressed fibrosis by preventing epithelial-mesenchymal transition and smooth muscle hyperplasia, and attenuated hyperalgesia by inhibiting mast cell degranulation. RSL3 exacerbated these pathological changes, whereas DFO attenuated them. Li-ESWT also suppressed oxidative stress and ferroptosis, as indicated by reduced reactive oxygen species and ferrous iron accumulation, lipid peroxidation, and ferroptosis-driving factors (ACSL4, LPCAT3, ALOX15, COX-2) levels. Li-ESWT also upregulated the Integrin-β1 and NRF2-xCT/GPX4 expression. In vitro, 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:
Li-ESWT ameliorates inflammation, fibrosis, hyperalgesia in the CP/CPPS model, likely through ferroptosis mitigation via activating the Integrin-β1/NRF2 pathway.
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