Altered expression of type I insulin-like growth factor receptor in Crohn's disease

Abstract

SummaryThe fibrotic and antiapoptotic effects of insulin-like growth factors (IGF) are mediated by type I IGF receptor (IGF-1R). IGFs could play a role in intestinal stricturing and in the maintenance of inflammation in Crohn's disease (CD). We aimed to describe IGF-1R expression in CD intestinal lesions, to compare it to other intestinal inflammatory diseases and to correlate it with fibrosis and apoptosis. IGF-1R expression and apoptosis (active caspase-3) were studied by immunohistochemistry. Surgical intestinal specimens [17 CD, nine controls, six diverticulitis and four ulcerative colitis (UC)] were used. IGF-1R was expressed transmurally mainly by inflammatory cells (IC) and smooth muscle cells, both in diseased intestine and controls. IGF-1R positive IC were increased in the mucosa and the submucosa of CD ( P < < < < 0·007), and in involved areas compared to uninvolved areas ( P = = = = 0·03). In UC, the number of IGF-1R positive IC was only increased in the mucosa, and was not different from controls in the submucosa. In diverticulitis, the number of IGF-1R positive IC did not differ from controls. In CD submucosa, IGF-1R expression in IC was inversely correlated with apoptosis in uninvolved areas ( P = = = = 0·01). Expression of IGF-1R in submucosal fibroblast-like cells, subserosal adipocytes and hypertrophic nervous plexi was specific for CD. We have shown a transmural altered expression of IGF-1R in CD. This may suggest a role for IGF-1R in the maintenance of chronic inflammation and stricture formation in CD.

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Insulin-like Growth Factor-1 Receptor Transactivation Modulates the Inflammatory and Proliferative Responses of Neurotensin in Human Colonic Epithelial Cells

“…IGF-1 regulates gastrointestinal tract growth and tissue repair as well as tumorigenesis through binding to its high-affinity receptor IGF-1R, which activates a number of signaling transduction pathways, including PI3K and downstream kinase Akt (34). IGF-1R is also altered in the intestines of Crohn disease patients (35), suggesting a possible role for IGF-1R in colitis. The PI3K/Akt pathway is involved not only in cell proliferation, differentiation, and survival but also in the NF-B-mediated pro-inflammatory effects of TNF␣ (36,37), IL-1␤ (38), and the GPCR B2-type bradykinin receptor (39).…”