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The alpha-smooth muscle actin promoter: a useful tool to analyse autocrine and paracrine roles of mesenchymal cells in normal and diseased bowel
  1. P K LUND
  1. Department of Physiology and
  2. Center for Gastrointestinal Biology and Disease,
  3. University of North Carolina, CB#7545,
  4. Chapel Hill, North Carolina 27599–7545, USA

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IGF-I mediates many of the postnatal growth promoting actions of pituitary derived growth hormone (GH) on multiple organs between birth and puberty and during adulthood.1 ,2 The bowel is now well established as an important target organ for GH and IGF-I.1 ,2 GH and IGF-I are currently being used in clinical trials to improve bowel function in patients with short bowel syndrome.3 ,4 IGF-I seems to mediate many of the enterotrophic actions of GH, which in turn increases circulating concentrations and local expression of IGF-I in bowel.2 ,5Previous studies in transgenic mice overexpressing metallothionen promoter I driven human IGF-I transgenes (MT-hIGF-I mice) or bovine GH transgenes (MT-bGH mice) revealed major increases in the mass of intestinal mucosa and in small bowel length relative to wild type.5 ,6 MT-hIGF-I mice have elevated circulating IGF-I, local overexpression of IGF-I in intestine and GH deficiency.6 Despite the deficiency in GH, MT-hIGF-I mice show similar or increased bowel growth compared with MT-bGH mice that have excess GH and IGF-1.6 Although studies on MT-bGH and MT-hIGF-I mice support the concept that IGF-I mediates most of the enterotrophic actions of GH, they did not tackle a key issue in IGF-I physiology—that is, the relative contributions of circulating versus locally expressed IGF-I in mediating bowel growth. A further limitation of the MT-hIGF-I mice is that the IGF-I transgene is expressed primarily in intestinal epithelial cells which are not the normal sites of endogenous IGF-I expression in bowel.6 A number of lines of evidence indicate that locally expressed, endogenous IGF-I contributes to normal or adaptive growth of bowel and is expressed throughout human and rodent bowel.7 ,8 Increased IGF-I expression in small bowel correlates with adaptive growth of bowel mucosa in response …

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