Loss of PINCH2 leads to myogenic urinary retention in mice.

AIMS: Myogenic urinary retention is a common urological disorder characterized by diminished detrusor contractility, reduced muscle mass, and disorganized muscle bundles, yet its molecular mechanisms are poorly defined. The adaptor protein PINCH2 is abundant in smooth muscle. This study aimed to determine whether the loss of PINCH2 induces myogenic urinary retention.

MATERIALS AND

METHODS

C57BL/6 wild-type (WT) and PINCH2 global knockout (KO) mice were used for urodynamic assessments, post-void residual (PVR) measurement, and detrusor smooth muscle (DSM) strip electrical field stimulation (EFS) for contractility. Bladder tissue was analyzed via Hematoxylin-eosin (HE), Van Gieson (VG), and immunofluorescent staining. PINCH2-knockdown human bladder detrusor smooth muscle cells (HBdSMCs) were used to detect Desmin expression, and serum cytokines in WT/KO mice were quantified with a Mouse Cytokine Array Kit.

KEY FINDINGS: PINCH2 KO mice developed progressive retention with increased PVR, reduced voiding efficiency, and impaired DSM contractility. Bladders showed thinner walls, disorganized muscle bundles, fewer fibers, and inflammatory infiltration. Desmin expression decreased in KO mouse bladders and PINCH2-knockdown HBdSMCs.

SIGNIFICANCE: PINCH2 deficiency induces myogenic retention by impairing detrusor contractility and reducing Desmin, representing a novel therapeutic target for detrusor underactivity.