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Am J Physiol Gastrointest Liver Physiol 273: G875-G882, 1997;
0193-1857/97 $5.00
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Vol. 273, Issue 4, G875-G882, October 1997

IGF-I induces collagen and IGFBP-5 mRNA in rat intestinal smooth muscle

E. M. Zimmermann1, L. Li1, Y. T. Hou1, M. Cannon1, G. M. Christman2, and K. N. Bitar3

Departments of 1 Internal Medicine, 2 Obstetrics and Gynecology, and 3 Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan 48109-0586

Insulin-like growth factor (IGF) binding protein 5 (IGFBP-5) mRNA was studied in intestines of rats with peptidoglycan-polysaccharide enterocolitis by Northern analysis and in situ hybridization. IGFBP-5 mRNA was increased 2.4 ± 0.5-fold in inflamed rat colon compared with controls and was highly expressed in smooth muscle. Cultured rat intestinal smooth muscle cells were used to study the regulation of IGFBP-5 and type I collagen synthesis. IGF-I (100 ng/ml) increased IGFBP-5 mRNA (1.9 ± 0.1-fold) and collagen type alpha 1(I) mRNA (1.6 ± 0.2-fold) in cultured smooth muscle cells. IGF-I induced a dose- and time-dependent increase in IGFBP-5 in conditioned medium by Western ligand blot and by immunoblot. IGF-I did not affect the IGFBP-5 mRNA decay rate after transcriptional blockade. Cycloheximide abolished IGFBP-5 mRNA. In conclusion, IGFBP-5 mRNA is expressed by intestinal smooth muscle and is increased during chronic inflammation. IGF-I increases IGFBP-5 and collagen mRNAs in intestinal smooth muscle cells.

inflammatory bowel disease; Crohn's disease; intestinal fibrosis; growth factors; insulin-like growth factor I; insulin-like growth factor binding protein 5


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