title: Insulin-like growth factor binding protein 3 in inflammatory bowel disease.
abstract: Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed as values of total protein, which is a sum of bioactive intact 43- to 45-kDa protein and its inactive proteolytic cleavage fragments. We aimed to assess the levels of intact IGFBP-3 and its cleaving protease MMP-9 in IBD. Patients with IBD and controls were included. Total plasma IGFBP-3 concentration was measured in ELISA. Western blot analysis, which distinguishes between intact and cleaved IGFBP-3, was performed in order to determine the ratio of intact to total protein; this ratio was used to calculate the concentration of intact IGFBP-3. The profile of plasma proteases was evaluated in zymography and MMP-9 levels were determined in ELISA. The concentration of intact IGFBP-3 was significantly decreased in patients with moderate to severe IBD activity compared to those in remission or controls. Of note, a dramatic depletion of intact IGFBP-3 was found in 7.4% of patients with IBD. Zymography revealed that the dominant gelatinase was the pro-form of MMP-9. However, no differences in MMP-9 levels were noted between those with active disease and controls. The level of intact IGFBP-3 is decreased in IBD patients with moderate to severe disease activity. This decrease may be linked to altered IGFBP-3 production or to increased cleavage by proteases other than MMP-9.
authors.affiliation: Department of Surgery, Columbia University, New York, New York, USA.
authors.forename: Irena
authors.initials: I
authors.lastname: Kirman
authors.forename: Richard Larry
authors.initials: RL
authors.lastname: Whelan
authors.forename: Suvinit
authors.initials: S
authors.lastname: Jain
authors.forename: Sara Elsøe
authors.initials: SE
authors.lastname: Nielsen
authors.forename: Jakob Benedict
authors.initials: JB
authors.lastname: Seidelin
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000503:physiopathology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009994:Osmolar Concentration; D010447:Peptide Hydrolases / Q000097:blood; D012720:Severity of Illness Index
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D010447:Peptide Hydrolases; D020780:Matrix Metalloproteinase 9