BACKGROUND: Radiation damage to the normal gut is a dose-limiting factor in the application of radiation therapy to treat abdominal and pelvic cancers. All tissue cell types react in concert to orchestrate an acute inflammatory reaction followed by a delayed chronic scarring process. Osteopontin (OPN) is a matricellular protein known to be involved in various physiological but also pathological processes such as tissue inflammation and fibrosis. AIMS: The aim of our study was to determine whether OPN knockout influences the severity of radiation proctitis and to investigate the role of OPN in the development of radiation-induced gut damage. RESULTS: Here we show that human radiation proctitis is associated with increased immunostaining of the intracellular and extracellular/matrix-linked isoforms of OPN. Moreover, endothelial cells in vitro and rectal tissue in a preclinical model of radiation proctitis in mice both respond to radiation exposure by a sustained increase in OPN mRNA and protein levels. Genetic deficiency of OPN did not influence radiation-induced rectal damage and was associated with significantly decreased animal survival. The acute and late radiation injury scores were similar in OPN-null mice compared with their control littermates. CONCLUSION: This study shows that in our model and given the pleiotropic actions of OPN in tissue inflammation and fibrosis, further studies are necessary to understand the precise roles of OPN in radiation-induced proctitis and to determine whether OPN is a useful therapeutic tool in prevention of radiation-induced intestinal tissue injury.
BACKGROUND: Radiation damage to the normal gut is a dose-limiting factor in the application of radiation therapy to treat abdominal and pelvic cancers. All tissue cell types react in concert to orchestrate an acute inflammatory reaction followed by a delayed chronic scarring process. Osteopontin (OPN) is a matricellular protein known to be involved in various physiological but also pathological processes such as tissue inflammation and fibrosis. AIMS: The aim of our study was to determine whether OPN knockout influences the severity of radiation proctitis and to investigate the role of OPN in the development of radiation-induced gut damage. RESULTS: Here we show that human radiation proctitis is associated with increased immunostaining of the intracellular and extracellular/matrix-linked isoforms of OPN. Moreover, endothelial cells in vitro and rectal tissue in a preclinical model of radiation proctitis in mice both respond to radiation exposure by a sustained increase in OPN mRNA and protein levels. Genetic deficiency of OPN did not influence radiation-induced rectal damage and was associated with significantly decreased animal survival. The acute and late radiation injury scores were similar in OPN-null mice compared with their control littermates. CONCLUSION: This study shows that in our model and given the pleiotropic actions of OPN in tissue inflammation and fibrosis, further studies are necessary to understand the precise roles of OPN in radiation-induced proctitis and to determine whether OPN is a useful therapeutic tool in prevention of radiation-induced intestinal tissue injury.
Authors: Hanne K Møller; Thomas Thymann; Lisbeth N Fink; Hanne Frokiaer; Anne S Kvistgaard; Per T Sangild Journal: Br J Nutr Date: 2010-08-20 Impact factor: 3.718
Authors: Marie Catherine Vozenin-Brotons; Fabien Milliat; Jean Christophe Sabourin; Anne Charlotte de Gouville; Agnès François; Philipe Lasser; Philipe Morice; Christine Haie-Meder; Antoine Lusinchi; Sami Antoun; Jean Bourhis; Denis Mathé; Theo Girinsky; Jocelyne Aigueperse Journal: Int J Radiat Oncol Biol Phys Date: 2003-06-01 Impact factor: 7.038
Authors: Meritxell Mollà; Meritxell Gironella; Rosa Miquel; Victoria Tovar; Pablo Engel; Albert Biete; Josep M Piqué; Julián Panés Journal: Int J Radiat Oncol Biol Phys Date: 2003-09-01 Impact factor: 7.038