Targeting ROCK1/YAP1 Axis Ameliorates Inflammation-Induced Prostatic Hyperplasia via Stabilising SIRT1-Dependent...

Area of Science:

• Urology
• Molecular Biology
• Pathology

Background:

• Benign prostatic hyperplasia (BPH) is a prevalent condition in aging men, often exacerbated by chronic inflammation and oxidative stress.
• The YAP1 protein, regulated by ROCK1, plays a role in organ size, cellular balance, and fibrosis, suggesting its potential involvement in BPH pathogenesis.

Purpose of the Study:

• To investigate the therapeutic potential of targeting the ROCK1/YAP1 signaling axis for mitigating BPH progression.
• To elucidate the molecular mechanisms by which YAP1 activation contributes to BPH development under inflammatory conditions.

Main Methods:

• Rats underwent prostate-specific YAP1 overexpression via adeno-associated virus (AAV) injection.
• An experimental autoimmune prostatitis (EAP) model was established and treated with ROCK1 inhibitor (fasudil) and YAP1 inhibitor (verteporfin).
• Cellular models were used to confirm YAP1's role in mitochondrial function.

Main Results:

• YAP1 overexpression induced BPH phenotypes, including inflammation, hyperplasia, fibrosis, and oxidative stress.
• Treatment with fasudil and verteporfin significantly alleviated BPH lesions in the EAP model.
• YAP1 activation suppressed SIRT1, impairing mitochondrial dynamics (DRP1/MFN2) and exacerbating oxidative stress.

Conclusions:

• Inflammation-driven activation of the ROCK1/YAP1 axis promotes BPH by increasing oxidative stress and impairing mitochondrial function.
• Targeting ROCK1 or YAP1 offers a promising preclinical strategy for treating inflammatory BPH.