Skip Navigation LinksHome > July 2014 - Volume 59 - Issue 1 > Smad3-Deficient Mice Have Reduced Esophageal Fibrosis and An...
Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0000000000000343
Original Articles: Gastroenterology

Smad3-Deficient Mice Have Reduced Esophageal Fibrosis and Angiogenesis in a Model of Egg-Induced Eosinophilic Esophagitis

Cho, Jae Youn*; Doshi, Ashmi*; Rosenthal, Peter*; Beppu, Andrew*; Miller, Marina*; Aceves, Seema; Broide, David*

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Abstract

Objectives: Eosinophilic esophagitis (EoE) is a food-triggered disease associated with esophageal fibrosis and stricture formation in a subset of patients. In the present study we used a murine model of egg (ovalbumin [OVA])–induced EoE to determine whether inhibiting transforming growth factor-β1 (TGF-β1) signaling through the Smad3 pathway would inhibit features of esophageal remodeling including fibrosis, angiogenesis, and basal zone hyperplasia.

Methods: Wild-type (WT) and Smad3-deficient (KO [knockout]) mice were sensitized intraperitoneally and then challenged chronically with intraesophageal OVA for 1 month. Levels of esophageal eosinophils, esophageal TGF-β1+ and vascular endothelial growth factor (VEGF)+ cells, and features of esophageal remodeling (fibrosis, angiogenesis, basal zone hyperplasia) were quantitated by immunohistochemistry and image analysis.

Results: OVA challenge induced a similar increase in the levels of esophageal major basic protein (MBP)+ eosinophils and esophageal TGF-β1+ cells in WT and Smad3 KO mice. Smad3 KO mice challenged with OVA had significantly less esophageal fibrosis and esophageal angiogenesis compared with OVA-challenged WT mice. The reduced esophageal angiogenesis in Smad3 KO mice was associated with reduced numbers of VEGF+ cells in the esophagus. There was a trend toward OVA-challenged Smad3 KO to have reduced basal zone hyperplasia, but this was not statistically significant.

Conclusions: In a mouse model of egg-induced EoE, Smad3-deficient mice have significantly less esophageal remodeling, especially fibrosis and angiogenesis that is associated with reduced expression of VEGF. Targeting the TGF-β1/Smad3 pathway may be a novel strategy to reduce esophageal fibrosis and its associated complications such as esophageal strictures in EoE.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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