PIEZO2 Expression Decreases in Bladder Smooth Muscle Cells of Males With Partial Bladder Outlet Obstruction and Its Role in Detrusor Underactivity

Overdistention of bladder smooth muscle cells (BSMCs) resulting from long-term complications of benign prostatic hyperplasia (BPH), such as urinary difficulty and increased bladder pressure, leads to progressive detrusor remodeling over time. With a high prevalence, myogenic detrusor underactivity (DU) represents an important etiological classification. However, the mechanisms by which over-stretch affects the detrusor remains unclear. Bladder smooth muscle cells play a critical role in detrusor contractility and structural remodeling. In this study, detrusor layer samples from DU patients and animal model were employed to investigate the hypothesis that mechanosensitive PIEZO2 channels contribute to regulation of stretch. Bladder neck ligation was performed to conduct the rat partial bladder outlet obstruction model. Cell stretch experiment was performed for creating an in vitro model of detrusor underactivity. Western blotting, PCR, and immunofluorescence staining were used to confirm the expression and location of PIEZO2 and marker proteins. We observed a decreased expression of PIEZO2 channels in the BSMCs of DU patients, followed by mitochondrial dysfunction. These findings suggest that functional PIEZO2 channels may underlie detrimental stretch-induced physical and functional alternations in the detrusor due to BPH.