Mesenchymal IGF-I overexpression: paracrine effects in the intestine, distinct from endocrine actions

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 di...

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Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2002-10, Vol.283 (4), p.G875-G885
Main Authors: Williams, Kristen L, Fuller, C Randall, Fagin, James, Lund, P Kay
Format: Article
Language:English
Subjects:
Actins - genetics
Animals
Colon - growth & development
Female
Gene Expression
Ileum - growth & development
Insulin-Like Growth Factor Binding Protein 3 - genetics
Insulin-Like Growth Factor Binding Protein 5 - genetics
Insulin-Like Growth Factor I - genetics
Intestinal Mucosa - chemistry
Intestinal Mucosa - drug effects
Intestinal Mucosa - growth & development
Intestines - chemistry
Intestines - growth & development
Intestines - metabolism
Jejunum - growth & development
Male
Mesoderm - chemistry
Mesoderm - metabolism
Mice
Mice, Transgenic
Muscle, Smooth - chemistry
Muscle, Smooth - growth & development
Promoter Regions, Genetic
Rats
RNA, Messenger - analysis
Sucrase - metabolism
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Summary: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 alpha-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.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.00089.2002