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

The 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.

[The IGF system: summary and recent data]. / Le système IGF: synthèse et données récentes.

We are entitled to state that our knowledge about the IGF system has literally exploded in the last years. Having been considered for some time merely as trophic and mitogenic factors, the IGFs now appear as molecules essential for the differentiation of many cell types, and even more so, as powerful protective agents for the nervous and the cardiovascular systems. However, these properties so beneficial in normal physiological conditions, are subverted by the cancerous cells who use them to extend their life span and resist therapy. The IGFs did not live up to expectations in the treatment of diabetes; however, today their capacity to improve the condition of patients suffering from severe neurological, renal or muscle diseases is tested. The IGF system might also be targetted by the anticancer treatments. In the following paper we have briefly summarized our knowledge on the IGF system, and presented in more detail the recent data.