Yuga Komaki1, Shuji Kanmura2, Fumisato Sasaki1, Hidehito Maeda1, Kohei Oda3, Shiho Arima1, Shiroh Tanoue1, Yuichiro Nasu1, Shinichi Hashimoto1, Seiichi Mawatari1, Hirohito Tsubouchi3,4, Akio Ido1. 1. Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. 2. Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan, skanmura@m2.kufm.kagoshima-u.ac.jp. 3. Department of HGF Tissue Repair and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. 4. Kagoshima City Hospital, Kagoshima, Japan.
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.
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.