Prolonged Peritoneal Gene Expression Using a Helper-Dependent Adenovirus Journal Articles

abstract

• BackgroundEncapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis. The causes of EPS are not well defined and are likely multifactorial. A suitable animal model would facilitate research into the pathophysiology and treatment of EPS.MethodsWe developed a helper-dependent adenovirus that expresses both green fluorescent protein (GFP) and active transforming growth factor-beta (TGF-β1; HDAdTGF-β1). Mice were administered HDAdTGF-β1 via intraperitoneal injection and the response was compared with mice administered either first-generation adenovirus expressing TGF-β1 (AdTGF-β1) or control adenovirus (AdGFP).ResultsHDAdTGF-β1-treated mice continued to express the GFP reporter transgene to day 74, the end of the observation period. Transgene expression lasted less than 28 days in the animals treated with first-generation adenoviruses. Animals treated with first-generation AdTGF-β1 demonstrated submesothelial thickening and angiogenesis at day 7, with almost complete resolution by day 28. The HDAdTGF-β1-treated mice demonstrated progressive peritoneal fibrosis with adhesion formation and encapsulation of bowels. Weight gain was significantly reduced in animals treated with HDAdTGF-β1 compared to both the control-treated animals and the AdTGF-β1-treated animals. Inflammation was not a major component of the fibroproliferative response.ConclusionsPeritoneal administration of a first-generation AdTGF-β1 leads to transient gene expression, resulting in a resolving fibrotic response and histology similar to that seen in simple peritoneal sclerosis. Prolonged TGF-β1 expression induced by the helper-dependent HDAdTGF-β1 led to changes in peritoneal morphology resembling EPS. This suggests that TGF-β1 may be a contributing factor in both simple peritoneal sclerosis and EPS. This model will be useful for elucidation of the mechanism of EPS and evaluation of potential treatment.

authors

• Liu, Limin
• Shi, Chang-Xin
• Ghayur, Ayesha
• Zhang, Claire
• Su, Je Yen
• Hoff, Catherine M
• Margetts, Peter

status

• published 

publication date

• September 2009

has subject area

• Adenoviridae (MeSH)
• Animals (MeSH)
• Gene Expression (MeSH)
• Gene Transfer Techniques (MeSH)
• Genetic Vectors (MeSH)
• Green Fluorescent Proteins (MeSH)
• Helper Viruses (MeSH)
• Mice (MeSH)
• Mice, Inbred C57BL (MeSH)
• Peritoneal Dialysis (MeSH)
• Peritoneal Fibrosis (MeSH)
• Peritoneum (MeSH)
• Transforming Growth Factor beta1 (MeSH)

published in

• Advances in peritoneal dialysis. Conference on Peritoneal Dialysis  Journal

keywords

• Adenoviridae
• Animals
• Gene Expression
• Gene Transfer Techniques
• Genetic Vectors
• Green Fluorescent Proteins
• Helper Viruses
• Mice
• Mice, Inbred C57BL
• Peritoneal Dialysis
• Peritoneal Fibrosis
• Peritoneum
• Transforming Growth Factor beta1

Digital Object Identifier (DOI)

• 10.1177/089686080902900507

PubMed ID

• 19776043

start page

• 508

end page

• 516

volume

• 29

issue

• 5