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1(I) are
coexpressed in a subset of mesenchymal cells in active Crohn's
disease
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
1(I) mRNAs. Masson's trichrome staining and
immunohistochemistry for IGF-I precursor,
-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
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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