BACKGROUND & AIMS: Cellular and molecular mechanisms of esophageal ulcer healing remain unexplored. We studied the sequential cellular events and the expression of keratinocyte growth factor (KGF) and its receptor (KGF-R) during the healing of experimental esophageal ulcers. METHODS: Esophageal ulcers were produced in rats by local application of acetic acid. Studies included (1) ulcer size, (2) quantitative histology, and (3) KGF and KGF-R messenger RNA and protein expression by reverse-transcription polymerase chain reaction, Western blotting, and immunostaining. In separate groups, ulcer size and esophageal epithelial proliferation were evaluated after a single injection of recombinant human KGF (1 mg/kg) around the ulcer. RESULTS: Ulcers were fully developed 3 days after induction, and 58% of ulcers were re-epithelialized by 9 days. At 3 days, in esophageal tissue bordering the ulcers, KGF messenger RNA and protein were increased by 191% and 151%, respectively, and KGF-R messenger RNA and protein were increased by 357% and 237%, respectively. KGF was expressed in stromal cells, whereas KGF-R was expressed in epithelial cells. At 6 days, epithelial proliferation at the ulcer margin was increased by 216%, and treatment with KGF further enhanced cell proliferation and accelerated ulcer healing. CONCLUSIONS: KGF is a likely mediator of esophageal epithelial proliferation and ulcer healing.
BACKGROUND & AIMS: Cellular and molecular mechanisms of esophageal ulcer healing remain unexplored. We studied the sequential cellular events and the expression of keratinocyte growth factor (KGF) and its receptor (KGF-R) during the healing of experimental esophageal ulcers. METHODS:Esophageal ulcers were produced in rats by local application of acetic acid. Studies included (1) ulcer size, (2) quantitative histology, and (3) KGF and KGF-R messenger RNA and protein expression by reverse-transcription polymerase chain reaction, Western blotting, and immunostaining. In separate groups, ulcer size and esophageal epithelial proliferation were evaluated after a single injection of recombinant humanKGF (1 mg/kg) around the ulcer. RESULTS:Ulcers were fully developed 3 days after induction, and 58% of ulcers were re-epithelialized by 9 days. At 3 days, in esophageal tissue bordering the ulcers, KGF messenger RNA and protein were increased by 191% and 151%, respectively, and KGF-R messenger RNA and protein were increased by 357% and 237%, respectively. KGF was expressed in stromal cells, whereas KGF-R was expressed in epithelial cells. At 6 days, epithelial proliferation at the ulcer margin was increased by 216%, and treatment with KGF further enhanced cell proliferation and accelerated ulcer healing. CONCLUSIONS:KGF is a likely mediator of esophageal epithelial proliferation and ulcer healing.
Authors: T Hayakawa; Y Fujiwara; M Hamaguchi; T Sugawa; M Okuyama; E Sasaki; T Watanabe; K Tominaga; N Oshitani; K Higuchi; T Arakawa Journal: Gut Date: 2005-10-06 Impact factor: 23.059
Authors: Amrita Ahluwalia; Dolgor Baatar; Michael K Jones; Andrzej S Tarnawski Journal: Am J Physiol Gastrointest Liver Physiol Date: 2014-07-24 Impact factor: 4.052
Authors: Dolgor Baatar; Michael K Jones; Koji Tsugawa; Rama Pai; Woo S Moon; Gou Y Koh; Injune Kim; Seigo Kitano; Andrzej S Tarnawski Journal: Am J Pathol Date: 2002-10 Impact factor: 4.307
Authors: Ahmed Salem; Hitesh Mistry; Alison Backen; Clare Hodgson; Pek Koh; Emma Dean; Lynsey Priest; Kate Haslett; Ioannis Trigonis; Alan Jackson; Marie-Claude Asselin; Caroline Dive; Andrew Renehan; Corinne Faivre-Finn; Fiona Blackhall Journal: Clin Lung Cancer Date: 2017-12-11 Impact factor: 4.785