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Departments of 1 Cell and Molecular Physiology and 2 Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7080; and 3 Division of Endocrinology and Metabolism, University of Cincinnati, Cincinnati, Ohio 45267
Local IGF-I expression is frequently
increased in intestinal mesenchyme during adaptive growth of intestinal
epithelium, but paracrine growth effects of IGF-I in vivo are not
defined. We tested whether overexpression of IGF-I in intestinal
mesenchyme increases epithelial growth and if effects are distinct from
known effects of circulating IGF-I. SMP8-IGF-I-transgenic (TG) mice overexpress IGF-I driven by an 
-smooth muscle actin promoter. Mucosal and muscularis growth were assessed in the jejunum, ileum, and
colon of SMP8-IGF-I-TG mice and wild-type littermates. Abundance of the
SMP8-IGF-I transgene and IGF binding protein (IGFBP)-3 and -5 mRNAs was
determined. Mucosal growth was increased in SMP8-IGF-I-TG ileum but not
jejunum or colon; muscularis growth was increased throughout the bowel.
IGFBP-5 mRNA was increased in SMP8-IGF-I-TG jejunum and ileum and was
specifically upregulated in ileal lamina propria. Overexpression of
IGF-I in intestinal mesenchymal cells has preferential paracrine
effects on the ileal mucosal epithelium and autocrine effects on the
muscularis throughout the bowel. Locally expressed IGF-I has distinct
actions on IGFBP expression compared with circulating IGF-I.
insulin-like growth factor-I; mucosa; intestinal growth; insulin-like growth factor binding protein-3; insulin-like growth factor binding protein-5
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