Abstract
Stress urinary incontinence (SUI) is one of the most prevalent pelvic floor disorders in women, and it is pathologically linked to collagen metabolism imbalance. Current treatments face limitations, including suboptimal efficacy and invasiveness. radiofrequency therapy (RF) therapy has emerged as a promising non-invasive approach, yet its precise mechanisms, particularly concerning collagen remodeling, remain inadequately elucidated.This study aimed to investigate the effects of RF on vaginal collagen metabolism in SUI rats and elucidate its underlying molecular mechanisms. An SUI rat model was created via vaginal dilation and bilateral ovariectomy. Rats were divided into Sham, SUI, SUI-No-RF, and SUI-RF (n = 7/group). The SUI-RF group received RF treatment (500 kHz, 2 W, 40 °C–42 °C) every 5 days for 3 sessions. At week 3 post-modeling, urodynamic measurements, Masson’s trichrome staining, immunofluorescence, Transmission Electron Microscopy (TEM), Western blot, and quantitative real-time polymerase chain reaction ( qPCR) were performed. Compared to the Sham group, SUI rats exhibited significantly reduced bladder leak point pressure (BLPP) and abdominal leak point pressure (ALPP) (p < 0.001). RF treatment markedly increased BLPP and ALPP in the SUI-RF group versus SUI-No-RF (p < 0.001), restoring urinary continence. Vaginal tissue in the SUI-RF group exhibited collagen volume fraction, elevated type III Collagen expression, and restored fibril alignment (p < 0.05). Mechanistically, RF treatment activated the Transforming Growth Factor-β1 (TGF-β1)/Smad2 pathway (increased TGF-β1 expression and Smad2 phosphorylation), upregulated tissue inhibitor of metalloproteinase 1 (TIMP1), and suppressed matrix metalloproteinase 9 (MMP9) expression (p < 0.05). RF therapy restores vaginal collagen architecture and continence function in SUI rats by activating the TGF-β1/Smad2 pathway and bidirectionally modulating the MMP9/TIMP1 equilibrium. These findings elucidate a molecular mechanism for RF therapy and support its further development as a non-invasive treatment for SUI. GRAPHICAL ABSTRACT: Proposed Mechanism of Radiofrequency (RF) Therapy for Stress Urinary Incontinence (SUI). Vaginal RF treatment delivers controlled thermal energy to the tissue. This stimulus is proposed to activate transforming growth factor-beta (TGF-β) signaling. TGF-β binding to its receptor leads to phosphorylation of Smad2 (P-Smad2) and its translocation into the nucleus. Within the nucleus, the activated Smad complex regulates gene expression, promoting the synthesis of type III collagen while inhibiting degradation pathways. This restoration of collagen architecture strengthens pelvic floor support, thereby improving urethral closure function and alleviating SUI. Created with BioRender.com [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10103-026-04879-4.