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

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2002-10, Vol.46 (4), p.G875-G885
• Main Authors: WILLIAMS, Kristen L, FULLER, C. Randall, FAGIN, James, LUND, P. Kay
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Endocrine system; Fundamental and applied biological sciences. Psychology; Hormones; Intestine. Mesentery; Mucous membrane; Proteins; Vertebrates: digestive system
• ISSN: 0193-1857; 1522-1547

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 alph-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.