Inhibition of LIMK reduces contraction and proliferation in bladder smooth muscle induced by TGF- β1.

Overactive bladder (OAB) significantly impacts quality of life and poses substantial healthcare costs. Despite current treatments, there is an unmet need for innovative therapeutic strategies due to limited efficacy and high discontinuation rates. Our study aimed to investigate the role of transforming growth factor-β1 (TGF-β1) in bladder smooth muscle contraction and the potential of Lim kinase (LIMK) inhibitors in reducing TGF-β1-induced effects, offering a novel approach to OAB treatment. We found elevated urinary TGF-β1 levels in benign prostate hyperplasia (BPH) patients with OAB compared to those without. TGF-β1 significantly enhanced acetylcholine-induced detrusor contractions in rat detrusor, which were attenuated by LIMK inhibitors (SR7826 and LIMKi3). TGF-β1 also induced actin cytoskeleton reorganization and increased proliferation inhuman bladder smooth muscle cells (HBSMCs), both of which were inhibited by LIMK inhibitors in a dose-dependent manner. In conclusion, TGF-β1 appears to play a critical role in the pathophysiology of OAB by promoting detrusor contraction and smooth muscle cell proliferation. Inhibition of LIMK represents a potential therapeutic strategy for OAB by countering TGF-β1-induced effects. Further in vivo studies are warranted to explore the clinical implications of these findings.