Hepatocyte Growth Factor Facilitates Esophageal Mucosal Repair and Inhibits the Submucosal Fibrosis in a Rat Model of Esophageal Ulcer

Digestion. 2019;99(3):227-238. doi: 10.1159/000491876. Epub 2018 Sep 18.

Abstract

Background/aims: Esophageal mucosal damage often causes scar tissue, leading to refractory stricture. The aim of this study was to clarify the effect of hepatocyte growth factor (HGF) on esophageal mucosal repair and fibrosis leading to stricture in a rat model of esophageal ulcer.

Methods: Esophageal ulcers were induced in rats by topical exposure of the lower esophageal serosa to acetic acid, followed by intraperitoneal administration of HGF (200 µg/day) using an osmotic pump for 7 days. The effect of HGF on esophageal mucosal injury was investigated macroscopically and microscopically. The effect of HGF on epithelial cell proliferation and the expression of genes closely associated with the development of fibrosis were also examined.

Results: The administration of HGF for 7 days led to a significant reduction in the ulcerative area and enhanced the proliferation of esophageal epithelial cells. HGF treatment significantly decreased the fibrosis, and subsequently attenuated not only the foreshortening but also the narrowing of the esophagus. The expression levels of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and matrix metalloproteinase (MMP)-2, -9 were significantly decreased among rats treated with HGF.

Conclusion: HGF facilitates the repair of esophageal mucosal injury and may also ameliorate the esophageal fibrosis, possibly through enhanced re-epithelization.

Keywords: Esophageal ulcer; Fibrosis; Hepatocyte growth factor; Matrix metalloproteinase; Mucosal repair; Tissue inhibitor of metalloproteinase.

MeSH terms

  • Acetic Acid / toxicity
  • Animals
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Esophageal Diseases / chemically induced
  • Esophageal Diseases / drug therapy*
  • Esophageal Diseases / pathology
  • Esophageal Mucosa / drug effects
  • Esophageal Mucosa / pathology*
  • Fibrosis / drug therapy
  • Hepatocyte Growth Factor / pharmacology*
  • Hepatocyte Growth Factor / therapeutic use
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Ulcer / chemically induced
  • Ulcer / drug therapy*
  • Ulcer / pathology

Substances

  • HGF protein, human
  • Recombinant Proteins
  • Hepatocyte Growth Factor
  • Acetic Acid