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

doi:10.1152/ajpgi.00089.2002

HOME

HELP

FEEDBACK

SUBSCRIPTIONS

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

Kristen L Williams¹^*, C. Randall Fuller², James Fagin³, and Pauline Kay Lund²

¹ Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
² Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC, USA
³ Division of Endocrinology and Metabolism, University of Cincinnati, Cincinnati, OH, USA

^* To whom correspondence should be addressed. E-mail: kristen_williams{at}med.unc.edu.

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 mice (SMP8-IGF-I-TG) 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 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.

This article has been cited by other articles:

A. P. Garrison, C. M. Dekaney, D. C. von Allmen, P. K. Lund, S. J. Henning, and M. A. Helmrath
Early but not late administration of glucagon-like peptide-2 following ileo-cecal resection augments putative intestinal stem cell expansion
Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G643 - G650.
[Abstract] [Full Text] [PDF]

X. Liu, S. G. Murali, J. J. Holst, and D. M. Ney
Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1794 - R1802.
[Abstract] [Full Text] [PDF]

D. W. Nelson, S. G. Murali, X. Liu, M. C. Koopmann, J. J. Holst, and D. M. Ney
Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1175 - R1184.
[Abstract] [Full Text] [PDF]

J. G. Simmons, Y. Ling, H. Wilkins, C. R. Fuller, A. J. D'Ercole, J. Fagin, and P. K. Lund
Cell-specific effects of insulin receptor substrate-1 deficiency on normal and IGF-I-mediated colon growth
Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G995 - G1003.
[Abstract] [Full Text] [PDF]

S. G. Murali, X. Liu, D. W. Nelson, A. K. Hull, M. Grahn, M. K. Clayton, J. E. Pintar, and D. M. Ney
Intestinotrophic effects of exogenous IGF-I are not diminished in IGF binding protein-5 knockout mice
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2144 - R2150.
[Abstract] [Full Text] [PDF]

F Rieder, J Brenmoehl, S Leeb, J Scholmerich, and G Rogler
Wound healing and fibrosis in intestinal disease
Gut, January 1, 2007; 56(1): 130 - 139.
[Full Text] [PDF]

C. Z. Michaylira, J. G. Simmons, N. M. Ramocki, B. P. Scull, K. K. McNaughton, C. R. Fuller, and P. K. Lund
Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic actions of IGF-I in vivo
Am J Physiol Gastrointest Liver Physiol, September 1, 2006; 291(3): G472 - G481.
[Abstract] [Full Text] [PDF]

S. Bellier, N. R. Da Silva, G. Aubin-Houzelstein, C. Elbaz, J.-M. Vanderwinden, and J.-J. Panthier
Accelerated intestinal transit in inbred mice with an increased number of interstitial cells of Cajal
Am J Physiol Gastrointest Liver Physiol, January 1, 2005; 288(1): G151 - G158.
[Abstract] [Full Text] [PDF]

J. F. Kuemmerle, K. S. Murthy, and J. G. Bowers
IGFBP-3 activates TGF-{beta} receptors and directly inhibits growth in human intestinal smooth muscle cells
Am J Physiol Gastrointest Liver Physiol, October 1, 2004; 287(4): G795 - G802.
[Abstract] [Full Text] [PDF]

A. W. Knott, R. J. Juno, M. D. Jarboe, S. A. Profitt, C. R. Erwin, E. P. Smith, J. A. Fagin, and B. W. Warner
Smooth muscle overexpression of IGF-I induces a novel adaptive response to small bowel resection
Am J Physiol Gastrointest Liver Physiol, September 1, 2004; 287(3): G562 - G570.
[Abstract] [Full Text] [PDF]

				X. Liu, S. G. Murali, J. J. Holst, and D. M. Ney Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1794 - R1802. [Abstract] [Full Text] [PDF]

				D. W. Nelson, S. G. Murali, X. Liu, M. C. Koopmann, J. J. Holst, and D. M. Ney Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1175 - R1184. [Abstract] [Full Text] [PDF]

				J. G. Simmons, Y. Ling, H. Wilkins, C. R. Fuller, A. J. D'Ercole, J. Fagin, and P. K. Lund Cell-specific effects of insulin receptor substrate-1 deficiency on normal and IGF-I-mediated colon growth Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G995 - G1003. [Abstract] [Full Text] [PDF]

				S. G. Murali, X. Liu, D. W. Nelson, A. K. Hull, M. Grahn, M. K. Clayton, J. E. Pintar, and D. M. Ney Intestinotrophic effects of exogenous IGF-I are not diminished in IGF binding protein-5 knockout mice Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2144 - R2150. [Abstract] [Full Text] [PDF]

				F Rieder, J Brenmoehl, S Leeb, J Scholmerich, and G Rogler Wound healing and fibrosis in intestinal disease Gut, January 1, 2007; 56(1): 130 - 139. [Full Text] [PDF]

				C. Z. Michaylira, J. G. Simmons, N. M. Ramocki, B. P. Scull, K. K. McNaughton, C. R. Fuller, and P. K. Lund Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic actions of IGF-I in vivo Am J Physiol Gastrointest Liver Physiol, September 1, 2006; 291(3): G472 - G481. [Abstract] [Full Text] [PDF]

				S. Bellier, N. R. Da Silva, G. Aubin-Houzelstein, C. Elbaz, J.-M. Vanderwinden, and J.-J. Panthier Accelerated intestinal transit in inbred mice with an increased number of interstitial cells of Cajal Am J Physiol Gastrointest Liver Physiol, January 1, 2005; 288(1): G151 - G158. [Abstract] [Full Text] [PDF]

				J. F. Kuemmerle, K. S. Murthy, and J. G. Bowers IGFBP-3 activates TGF-{beta} receptors and directly inhibits growth in human intestinal smooth muscle cells Am J Physiol Gastrointest Liver Physiol, October 1, 2004; 287(4): G795 - G802. [Abstract] [Full Text] [PDF]

				A. W. Knott, R. J. Juno, M. D. Jarboe, S. A. Profitt, C. R. Erwin, E. P. Smith, J. A. Fagin, and B. W. Warner Smooth muscle overexpression of IGF-I induces a novel adaptive response to small bowel resection Am J Physiol Gastrointest Liver Physiol, September 1, 2004; 287(3): G562 - G570. [Abstract] [Full Text] [PDF]