title: Osteopontin knockout does not influence the severity of rectal damage in a preclinical model of radiation proctitis in mice.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Research Laboratory in Radiobiology and Radiopathology, Institute for Radiological Protection and Nuclear Safety, SRBE/L3R, 31 Avenue de la Division Leclerc, 92265, Fontenay-aux-Roses, France.
authors.forename: Karl
authors.initials: K
authors.lastname: Blirando
authors.forename: Elodie
authors.initials: E
authors.lastname: Mintet
authors.forename: Valérie
authors.initials: V
authors.lastname: Buard
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Fabien
authors.initials: F
authors.lastname: Milliat
authors.forename: Agnès
authors.initials: A
authors.lastname: François
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007124:Immunoenzyme Techniques; D015601:Injury Severity Score; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin / Q000378:metabolism*; D011349:Proctitis / Q000209:etiology* / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D011832:Radiation Injuries / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012004:Rectal Neoplasms / Q000532:radiotherapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053495:Osteopontin; D012313:RNA