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.

Local IGFBP-3 mRNA expression, apoptosis and risk of colorectal adenomas

“…IGF complexes also exist as approximately 50 kDA complexes comprising IGFs and IGFBPs that can exit capillaries. IGFBP-3 exists as a 43–45 kDa isoform with high affinity for the IGFs or as an inactive 30 kDa proteolytic cleaved fragment [ 1 , 3 , 4 ].…”

Insulin-Like Growth Factor Binding Protein-3 Inhibits Colitis-Induced Carcinogenesis

“…15 It has been noted that in the general population, after controlling for IGF-1 levels, a lower IGFBP-3 concentration is associated with a greater risk of colon cancer development. 33 It remains to be shown whether a significant decrease in circulating intact IGFBP-3 levels is a risk factor for the development of colon cancer in the setting of IBD.…”

“…[12][13][14] In addition we have previously shown that patients with moderate-to-severe IBD have a significant depletion of circulating intact IGFBP-3. 15 This study was designed to determine whether the maintenance of circulating intact IGFBP-3 levels can protect against the development of colonic tumors in the setting of colitis in a murine model.…”