Ting Fu1, Hubert Kalbacher, Werner Hoffmann. 1. Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke-University Magdeburg, Germany.
Abstract
BACKGROUND/AIMS: The trefoil factor family (TFF) peptide TFF1 is typically secreted by gastric surface mucous cells. These cells are also the major players in gastric restitution, i.e., repair of the stomach mucosa by cell migration after injury. METHODS: An established in vitro model of gastric restitution, i.e., migration of the non-transformed rat gastric cell line RGM-1 after scratch wounding, was investigated by expression profiling of selected genes from separated stationary and migratory cells. Also semi-quantitative immunocytochemistry was performed. Furthermore, RGM-1 cells were transfected with stealth RNAi™ duplexes targeting Tff1 and relative cell migration rates were analyzed. RESULTS: Surprisingly, Tff1 expression was up-regulated in migratory cells. No unequivocal signs of the epithelial-mesenchymal transition were detectable in migratory cells. Transfection of RGM-1 cells with Tff1-siRNAi duplexes negatively influenced migration of these cells. CONCLUSION: This clearly points to a function of Tff1 as a motogen. A possible up-regulation of TFF1 synthesis in migratory surface mucous cells also in vivo would be an ideal mechanism to specifically enhance gastric restitution only where topologically needed and to minimize eventual negative side effects of TFF1 such as cell scattering and invasiveness.
BACKGROUND/AIMS: The trefoil factor family (TFF) peptide TFF1 is typically secreted by gastric surface mucous cells. These cells are also the major players in gastric restitution, i.e., repair of the stomach mucosa by cell migration after injury. METHODS: An established in vitro model of gastric restitution, i.e., migration of the non-transformed rat gastric cell line RGM-1 after scratch wounding, was investigated by expression profiling of selected genes from separated stationary and migratory cells. Also semi-quantitative immunocytochemistry was performed. Furthermore, RGM-1 cells were transfected with stealth RNAi™ duplexes targeting Tff1 and relative cell migration rates were analyzed. RESULTS: Surprisingly, Tff1 expression was up-regulated in migratory cells. No unequivocal signs of the epithelial-mesenchymal transition were detectable in migratory cells. Transfection of RGM-1 cells with Tff1-siRNAi duplexes negatively influenced migration of these cells. CONCLUSION: This clearly points to a function of Tff1 as a motogen. A possible up-regulation of TFF1 synthesis in migratory surface mucous cells also in vivo would be an ideal mechanism to specifically enhance gastric restitution only where topologically needed and to minimize eventual negative side effects of TFF1 such as cell scattering and invasiveness.