TY - JOUR AU - Lund, P. Kay AB - Abstract 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 α1(I) mRNAs. Masson's trichrome staining and immunohistochemistry for IGF-I precursor, α-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 α1(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 Footnotes This work was facilitated by the Molecular Biology and Histopathology Core Facilities of the Center for Gastrointestinal Biology and Disease (National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-34987) and supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-02402 (to J. B. Pucilowska), DK-40249 (to R. B. Sartor), and DK-47769 (to P. K. Lund). Address for reprint requests and other correspondence: J. B. Pucilowska, Dept. of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7545 (E-mail: jola@med.unc.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 2000 the American Physiological Society TI - IGF-I and procollagen α1(I) are coexpressed in a subset of mesenchymal cells in active Crohn's disease JO - AJP - Gastrointestinal and Liver Physiology DA - 2000-12-01 UR - https://www.deepdyve.com/lp/the-american-physiological-society/igf-i-and-procollagen-1-i-are-coexpressed-in-a-subset-of-mesenchymal-HRdP9DM5B9 VL - 279 IS - 6 DP - DeepDyve ER -