A phenotype of IGFBP-3 knockout mice revealed by dextran sulfate-induced colitis.

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.

• Authors: Debbie Yancu, Marie-José Blouin, Elena Birman, Livia Florianova, Olga Aleynikova, Mahvash Zakikhani, Heather VanderMeulen, Ernest Seidman, Michael Pollak
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 32 Issue 1 Pg. 146-153 (Jan 2017) ISSN: 1440-1746 [Electronic] Australia
• PMID: 27253188 (Publication Type: Journal Article)
• Copyright: © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Insulin-Like Growth Factor Binding Protein 3
• Dextran Sulfate

Topics

• Animals
• Colitis, Ulcerative (chemically induced, genetics)
• Dextran Sulfate (adverse effects)
• Disease Models, Animal
• Female
• Insulin-Like Growth Factor Binding Protein 3 (genetics)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Phenotype
• Severity of Illness Index