A phenotype of IGFBP‐3 knockout mice revealed by dextran sulfate‐induced colitis. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Yancu, Debbie; Blouin, Marie‐José; Birman, Elena; Florianova, Livia; Aleynikova, Olga; Zakikhani, Mahvash; VanderMeulen, Heather; Seidman, Ernest; Pollak, Michael
• Is Part Of: Journal of gastroenterology and hepatology. Volume 32:Issue 1(2017)
• Page Start: 146
• Page End: 153
• Publication Date: 2017-01
• Subjects: dextran sulfate sodium -- insulin‐like growth factor binding protein‐3 -- ulcerative colitis; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Liver Diseases -- Periodicals; 616.33
• DOI: 10.1111/jgh.13461
• Languages: English
• ISSNs: 0815-9319

Abstract

Abstract: Background and Aim: 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. Conclusion: 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.