Pressure-mediated mechanosensitive Piezo2 channel is activated in neurogenic bladder and promote bladder fibrosis in children.

Mechanosensitive Piezo2 channels play a critical role in bladder pressure perception and may contribute to bladder fibrosis in patients with neurogenic bladder (NB), a condition that significantly affects quality of life. This study aimed to investigate the expression of Piezo2 and its role in bladder fibrosis using both human and animal models. Bladder tissue samples were obtained from children with NB undergoing ileocystoplasty, along with normal tissues from control subjects. An NB model was established in juvenile Sprague-Dawley rats through spinal nerve transection. Transcriptome analysis revealed the activation of pathways associated with mechanical stimulation, nuclear factor kappa-B (NF-κB) signaling, and epithelial-mesenchymal transition (EMT) in the context of NB. The results indicated that elevated Piezo2 levels were correlated with increased bladder pressure and fibrosis. Cystometry tests demonstrated significant increases in bladder pressure at week 2, followed by slight decreases, although pressure levels remained elevated compared to controls. Stretching experiments conducted on SV-HUC-1 cells showed that Piezo2 activation exacerbated fibrosis through the Ca²⁺/NF-κB/EMT axis, while the use of Piezo2 siRNA mitigated this effect. These findings suggest that Piezo2 channels, activated by increased pressure, accelerate bladder fibrosis via the Ca²⁺/NF-κB/EMT pathway, indicating that Piezo2 inhibition may serve as a potential therapeutic strategy to prevent fibrosis in NB.