Differential regulation by TGF-beta 1 and insulin of insulin-like growth factor binding protein-2 in IEC-6 cells

Autor: Courtney M. Townsend, Yan-Shi Guo, R. D. Beauchamp, Gui-Fang Jin, J. C. Thompson
Rok vydání: 1995
Předmět:
Zdroj: American Journal of Physiology-Endocrinology and Metabolism. 268:E1199-E1204
ISSN: 1522-1555
0193-1849
Popis: 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-beta 1 (TGF-beta 1) 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-beta 1 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 microgram/ml) also increased IGFBP levels in the CM of IEC-6 cells, but a high dose of insulin (10 micrograms/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-beta 1 (2.0 ng/ml) and suppressed by insulin (5.0 micrograms/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-beta 1 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-beta 1-stimulated production of IGFBP may contribute to the growth-inhibitory action in intestinal epithelial cells.x
Databáze: OpenAIRE