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Updated: Jun 28, 2026

Ex Vivo Analysis of Mechanically Activated Ca2+ Transients in Urothelial Cells
Published on: September 28, 2022
Excessive epithelial mechanosensation drives nociceptive innervation and chronic bladder pain via the
Min Jung Kim1, Joo Hwan Noh1, Ho Young Lee1
1Division of Life Sciences, Korea University, Seoul 02841, South Korea.
Abstract:
Epithelial mechanosensation maintains tissue homeostasis by sensing mechanical stimuli. Dysregulated mechanotransduction has been implicated in chronic pain, yet the molecular link between epithelial stress and persistent sensory dysfunction remains unclear. Here, we report that the mechanosensitive ion channel PIEZO1 is markedly upregulated in bladder epithelial cells under recurrent uropathogenic E. coli infection through interleukin-6 (IL-6)-dependent signaling. PIEZO1 overexpression amplifies mechanotransduction-induced reactive oxygen species (ROS) generation, triggering a homeostatic antioxidant response via the cystine-glutamate antiporter system Xc⁻ (SLC7A11). This protective mechanism inadvertently promotes extracellular glutamate accumulation, driving aberrant sprouting and hyperinnervation of peptidergic nociceptive C fibers into the epithelial layer. This neuroepithelial remodeling sensitizes bladder afferents and induces persistent pain-like states resembling chronic visceral pain and organ dysfunction. Our findings reveal a paradoxical role of epithelial antioxidant defense in promoting pain through the PIEZO1-SLC7A11-glutamate axis and highlight the neuroepithelial interface as a key therapeutic target for infection-induced chronic pain syndromes.
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