Prolonged peritoneal gene expression using a helper-dependent adenovirus

Area of Science:

• Biomedical Research
• Animal Models
• Gastroenterology

Background:

• Encapsulating peritoneal sclerosis (EPS) is a rare, multifactorial complication of peritoneal dialysis.
• The exact causes of EPS remain poorly understood.
• A robust animal model is crucial for studying EPS pathophysiology and developing treatments.

Purpose of the Study:

• To develop and validate a novel animal model for encapsulating peritoneal sclerosis (EPS).
• To investigate the role of prolonged transforming growth factor-beta 1 (TGF-beta1) expression in EPS development.
• To establish a platform for evaluating potential therapeutic interventions for EPS.

Main Methods:

• A helper-dependent adenovirus (HDAdTGF-beta1) expressing TGF-beta1 and GFP was engineered.
• Mice received intraperitoneal injections of HDAdTGF-beta1, first-generation AdTGF-beta1, or control AdGFP.
• Peritoneal response, transgene expression duration, and histological changes were monitored.

Main Results:

• HDAdTGF-beta1 induced sustained transgene expression (over 74 days) compared to transient expression (<28 days) with first-generation adenovirus.
• HDAdTGF-beta1 treatment resulted in progressive peritoneal fibrosis, adhesion formation, and bowel encapsulation.
• Mice treated with HDAdTGF-beta1 showed significantly reduced weight gain and minimal inflammation.

Conclusions:

• Prolonged TGF-beta1 expression via HDAdTGF-beta1 effectively models the peritoneal morphology of EPS.
• Transient TGF-beta1 expression led to a resolving fibrotic response, mimicking simple peritoneal sclerosis.
• This novel HDAdTGF-beta1 model provides a valuable tool for understanding EPS mechanisms and testing treatments.