The role of Piezo1 as a mechanotransduction hub in bladder fibrosis: therapeutic targeting strategies and challenges—a narrative review

Background and Objective: Bladder fibrosis represents an irreversible pathological endpoint in various urological disorders, including neurogenic bladder (NGB) and partial bladder outlet obstruction (PBOO), leading to severe voiding dysfunction. Current therapies fail to reverse established fibrosis, highlighting the urgent need for upstream therapeutic targets. This review aims to synthesize current knowledge on the role of Piezo1, a mechanosensitive ion channel, as a central mechanotransduction hub in bladder fibrosis pathogenesis, and to evaluate potential therapeutic strategies targeting this channel.

Methods: We conducted a comprehensive literature search of PubMed, Web of Science, and Scopus databases for studies published between January 2010 and June 2026 examining Piezo1’s role in bladder pathophysiology, mechanotransduction, and fibrotic mechanisms.

Key Content and Findings: Piezo1 directly translates pathological pressure overload into intracellular signals through Ca²⁺ influx, triggering fibroblast activation and myofibroblast differentiation. Piezo1 activation synergistically activates pro-fibrotic TGF-β1/Smad and Hippo/YAP1 pathways—key drivers of fibrosis progression. However, therapeutic targeting faces significant challenges due to Piezo1’s vital physiological roles in cardiovascular pressure sensing and renal fluid homeostasis, raising off-target risks with non-selective inhibition. Emerging strategies include allosteric modulators targeting unique Piezo1 domains, local intravesical delivery systems, and targeting Piezo1-interacting regulatory proteins to block pathological signaling while preserving physiological functions.

Conclusions: Piezo1 represents a novel upstream therapeutic target for bladder fibrosis. Future “smart” therapeutics targeting Piezo1-specific pathological signaling while preserving physiological functions offer new hope for end-stage bladder diseases. Further research on Piezo1-specific modulators and interactome mapping is warranted.