Partial bladder outlet obstruction in mice may cause E-cadherin repression through hypoxia induced pathway

Area of Science:

• Urology
• Pediatric Nephrology
• Molecular Biology

Background:

• Posterior urethral valves (PUV) are a primary cause of pediatric bladder outlet obstruction.
• PUV can lead to severe complications including incontinence, neurogenic bladder, and renal impairment.
• A significant portion of patients develop end-stage renal disease or persistent incontinence.

Purpose of the Study:

• To investigate the pathological consequences of partial bladder outlet obstruction (PBOO).
• To elucidate the underlying molecular mechanisms associated with PBOO.
• To establish a mouse model for studying PBOO.

Main Methods:

• Male C57BL/6 mice underwent surgical induction of PBOO or sham operation.
• Bladders and kidneys were collected at various time points post-surgery (1-7 days).
• Histological and biochemical analyses were performed to assess alterations and gene expression.

Main Results:

• PBOO mice showed increased bladder mass and urinary retention compared to controls.
• Obstruction led to bladder fibrosis and upregulation of profibrotic genes.
• Hypoxia-inducible factors and epithelial-mesenchymal transition factors were activated, with decreased E-cadherin.

Conclusions:

• PBOO induces significant histological and molecular changes in the mouse bladder.
• Activation of the hypoxia-inducible factors pathway is a key finding.
• Hypoxia-inducible factors may play a crucial role in the pathogenesis of PBOO via epithelial-mesenchymal transition.