IGF-I and procollagen alpha 1(I) are coexpressed in a subset of mesenchymal cells in active Crohn's disease

This study tested the hypothesis that insulin-like growth factor I (IGF-I) expression is increased at sites of fibrosis in diseased intestine of patie nts with Crohn's disease (CD). IGF-I mRNA was quantified by RNase protectio n assay in uninvolved and involved intestine of 13 CD patients (10 ileum, 3 colon) and 7 ulcerative colitis (UC) patients (colon). In situ hybridizati on histochemistry compared the localization of IGF-I and procollagen alpha1 (I) mRNAs. Masson's trichrome staining and immunohistochemistry for IGF-I p recursor, alpha -smooth muscle actin (A), vimentin (V), desmin (D), and c-k it were used to examine the mesenchymal cell subtypes that express IGF-I an d collagen in uninvolved and involved ileum and colon of CD patients and "n ormal" ileum and colon from noninflammatory controls. IGF-I mRNA was elevat ed in involved ileum and colon of patients with CD but not in involved colo n of patients with UC. IGF-I and procollagen alpha1(I) mRNA showed overlapp ing distribution within fibrotic submucosa and muscularis propria of involv ed CD ileum and colon. In involved CD intestine, increased IGF-I precursor expression localized to mesenchymal cells in regions of tissue disorganizat ion and fibrosis in muscularis mucosa, submucosa, and muscularis propria. I n these regions, there were increased numbers of V+ cells relative to norma l or uninvolved intestine. Increased IGF-I expression was localized to cell s with a phenotype typical of fibroblasts (V+/A(-)/D-), myofibroblasts (V+/ A(+)/D+), and, to a lesser extent, cells with normal enteric smooth muscle phenotype (V-/A(+)/D+). We conclude that increased IGF-I expression in mult iple mesenchymal cell subtypes and increased numbers of cells with fibrobla st/myofibroblast phenotype are involved in fibrosis associated with CD.