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 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.
Williams
Kristen L
KL
Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599-7080, USA. kristen_williams@med.unc.edu
Fuller
C Randall
CR
Fagin
James
J
Lund
P Kay
PK
D000199:Actins / Q000235:genetics*; D000818:Animals; D003106:Colon / Q000254:growth & development; D005260:Female; D015870:Gene Expression; D007082:Ileum / Q000254:growth & development; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D007422:Intestines / Q000737:chemistry / Q000254:growth & development*; D007583:Jejunum / Q000254:growth & development; D008297:Male; D008648:Mesoderm / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000737:chemistry / Q000254:growth & development; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013393:Sucrase / Q000378:metabolism
D000199:Actins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013393:Sucrase