title: A phenotype of IGFBP-3 knockout mice revealed by dextran sulfate-induced colitis.
abstract: OBJECTIVE
  Insulin-like growth factor-1 (IGF-1) bioactivity has been shown to be attenuated by insulin-like growth factor binding protein-3 (IGFBP-3), one of six IGF-binding proteins. While prior work revealed no major phenotype associated with IGFBP-3 knockout mice, we explored the possibility that a phenotype could be revealed under specific conditions of gastrointestinal stress.
  
  
  METHODS
  The dextran sodium sulfate (DSS) murine model of ulcerative colitis was used for this study.
  
  
  RESULTS
  Insulin-like growth factor binding protein-3 knockout mice had significantly reduced colitis on exposure to DSS as measured by lower levels of pro-inflammatory cytokines IL-6 (P < 0.0001), TNF-α (P = 0.0035), and IL-1β (P = 0.0112), reduced weight loss (P < 0.0001), reduced myeloperoxidase activity (P = 0.0025), and maintenance of colorectal length (P < 0.05), all relative to wild-type mice exposed to DSS. IGFBP-3 knockout mice also exhibited increased colon epithelial cell proliferation (P < 0.0001) following DSS exposure. Semi-quantitative immunohistochemistry showed greater IGF-1 receptor activation in colon epithelial cells of IGFBP-3 knockout mice compared with control mice following DSS exposure.
  
  
  CONCLUSIONS
  Our data demonstrate that IGFBP-3 influences severity of DSS-induced colitis. The observations suggest that in the absence of IGFBP-3, enhanced IGF bioactivity leads to increased epithelial proliferation and mucosal barrier repair, thereby lessening inflammation.
authors.affiliation: Segal Cancer Center, Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.|Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Debbie
authors.initials: D
authors.lastname: Yancu
authors.affiliation: Segal Cancer Center, Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Blouin
authors.affiliation: Segal Cancer Center, Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Birman
authors.affiliation: Department of Pathology McGill University Health Center, McGill University, Montreal, Quebec, Canada.
authors.forename: Livia
authors.initials: L
authors.lastname: Florianova
authors.affiliation: Department of Pathology McGill University Health Center, McGill University, Montreal, Quebec, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Aleynikova
authors.affiliation: Segal Cancer Center, Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Mahvash
authors.initials: M
authors.lastname: Zakikhani
authors.affiliation: Segal Cancer Center, Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.|Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: VanderMeulen
authors.affiliation: McGill Center for IBD Research Research Institute of the McGill University Health Center, McGill University, Montreal, Quebec, Canada.
authors.forename: Ernest
authors.initials: E
authors.lastname: Seidman
authors.affiliation: Segal Cancer Center, Lady Davis Institute of Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.|Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.|Department of Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000235:genetics*; D016264:Dextran Sulfate / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D016264:Dextran Sulfate
keywords: dextran sulfate sodium; insulin-like growth factor binding protein-3; ulcerative colitis