Differential regulation by TGF-β1 and insulin of insulin-like growth factor binding protein-2 in IEC-6 cells

Y. S. Guo, C. M. Townsend, G. F. Jin, R. D. Beauchamp, J. C. Thompson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The purposes of this study were to determine the regulation of insulin- like growth factor binding protein-2 (IGFBP-2) in IEC-6 cells by transforming growth factor-β1 (TGF-β1) and insulin and to determine whether IGFBP-2 mediated the growth-inhibitory action on the cells. Utilizing Western ligand blot analysis, we found that TGF-β1 at concentrations of 0.5, 1.0, and 2 ng/ml significantly increased levels of 32-kDa IGFBP in the conditioned medium (CM) of IEC-6 cells in a dose-dependent fashion and that low doses of insulin (1.0 and 5.0 μg/ml) also increased IGFBP levels in the CM of IEC-6 cells, but a high dose of insulin (10 μg/ml) depressed IGFBP release in the CM. Immunoblotting has shown that the IGFBP of 32 kDa was IGFBP-2 and further confirmed the above results. IGFBP-2 mRNA levels were stimulated by TGF-β1 (2.0 ng/ml) and suppressed by insulin (5.0 μg/ml). In addition, des (1-3) IGF-I (50 ng/ml) and insulin stimulated the proliferation of IEC-6 cells. Anti-IGFBP-2 antibodies partially blocked the inhibitory role in IEC-6 cell growth evoked by des (1-3) IGF-I. These findings suggest that the upregulation of IGFBP-2 by TGF-β1 occurs, at least in part, at the level of mRNA, whereas the regulation by insulin appears to be at a posttranslational level, and that the TGF-β1-stimulated production of IGFBP may contribute to the growth-inhibitory action in intestinal epithelial cells.

Original languageEnglish (US)
Pages (from-to)E1199-E1204
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume268
Issue number6 31-6
DOIs
StatePublished - 1995

Keywords

  • transforming growth factor-β1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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