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Am J Physiol Gastrointest Liver Physiol 279: G1307-G1322, 2000;
0193-1857/00 $5.00
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Vol. 279, Issue 6, G1307-G1322, December 2000

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

Jolanta B. Pucilowska1,2, Kirk K. McNaughton1, Nirupama K. Mohapatra1,2, Eileen C. Hoyt1,2, Ellen M. Zimmermann3, R. Balfour Sartor2,4, and P. Kay Lund1,2

1 Department of Cell and Molecular Physiology, 2 Center for Gastrointestinal Biology and Disease, and 4 Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545; and 3 Department of Medicine, University of Michigan, Ann Arbor, Michigan 48109-0586

This study tested the hypothesis that insulin-like growth factor I (IGF-I) expression is increased at sites of fibrosis in diseased intestine of patients with Crohn's disease (CD). IGF-I mRNA was quantified by RNase protection assay in uninvolved and involved intestine of 13 CD patients (10 ileum, 3 colon) and 7 ulcerative colitis (UC) patients (colon). In situ hybridization histochemistry compared the localization of IGF-I and procollagen alpha 1(I) mRNAs. Masson's trichrome staining and immunohistochemistry for IGF-I precursor, alpha -smooth muscle actin (A), vimentin (V), desmin (D), and c-kit were used to examine the mesenchymal cell subtypes that express IGF-I and collagen in uninvolved and involved ileum and colon of CD patients and "normal" ileum and colon from noninflammatory controls. IGF-I mRNA was elevated in involved ileum and colon of patients with CD but not in involved colon of patients with UC. IGF-I and procollagen alpha 1(I) mRNA showed overlapping distribution within fibrotic submucosa and muscularis propria of involved CD ileum and colon. In involved CD intestine, increased IGF-I precursor expression localized to mesenchymal cells in regions of tissue disorganization and fibrosis in muscularis mucosa, submucosa, and muscularis propria. In these regions, there were increased numbers of V+ cells relative to normal or uninvolved intestine. Increased IGF-I expression was localized to cells 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 multiple mesenchymal cell subtypes and increased numbers of cells with fibroblast/myofibroblast phenotype are involved in fibrosis associated with CD.

intestinal fibrosis; mesenchymal cells


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