Bushman T L, Kuemmerle J F
Departments of Medicine and Physiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0711, USA.
Am J Physiol. 1998 Dec;275(6):G1282-90. doi: 10.1152/ajpgi.1998.275.6.G1282.
Insulin-like growth factor-I (IGF-I)-mediated growth of cells can be modulated by specific IGF binding proteins (IGFBPs) that inhibit or augment IGF-I ligand-receptor interaction. IGFBP expression and production by human intestinal muscle cells in culture was characterized in rapidly growing cells (day 3 of culture), in confluent cells (day 7), and in postconfluent cells (day 14). RT-PCR analysis identified IGFBP-3, IGFBP-4, and IGFBP-5 mRNA during all three phases of growth. The production of IGFBP-3 and IGFBP-5 was regulated in reciprocal fashion. IGFBP-5 production was high on day 3 and decreased two- to fivefold by day 14, and IGFBP-3 production was low on day 3 and increased five- to eightfold by day 14. IGFBP-4 production remained constant. IGFBP-3 inhibited and IGFBP-5 augmented IGF-I-induced proliferation. IGFBP-3 and IGFBP-5 production was regulated in reciprocal fashion by transforming growth factor-beta1 (TGF-beta1). Immunoneutralization of endogenous TGF-beta1 decreased the production of IGFBP-3 and increased the production of IGFBP-5. Addition of exogenous recombinant human TGF-beta1 had the opposite effect. We conclude that the expression and time-dependent production of IGFBP-3, IGFBP-4, and IGFBP-5 and their regulation by endogenous TGF-beta1 represent mechanisms by which human intestinal muscle cells regulate autocrine IGF-I-mediated growth.
胰岛素样生长因子-I（IGF-I）介导的细胞生长可被特定的IGF结合蛋白（IGFBPs）调节，这些蛋白可抑制或增强IGF-I配体与受体的相互作用。对培养的人肠道肌肉细胞在快速生长的细胞（培养第3天）、汇合细胞（第7天）和汇合后细胞（第14天）中的IGFBP表达和产生情况进行了表征。RT-PCR分析在生长的所有三个阶段均鉴定出IGFBP-3、IGFBP-4和IGFBP-5的mRNA。IGFBP-3和IGFBP-5的产生呈相反的调节方式。IGFBP-5在第3天产生量高，到第14天下降了2至5倍，而IGFBP-3在第3天产生量低，到第14天增加了5至8倍。IGFBP-4的产生保持恒定。IGFBP-3抑制而IGFBP-5增强IGF-I诱导的增殖。IGFBP-3和IGFBP-5的产生受到转化生长因子-β1（TGF-β1）的相反调节。内源性TGF-β1的免疫中和降低了IGFBP-3的产生并增加了IGFBP-5的产生。添加外源性重组人TGF-β1则产生相反的效果。我们得出结论，IGFBP-3、IGFBP-4和IGFBP-5的表达、时间依赖性产生及其受内源性TGF-β1的调节代表了人肠道肌肉细胞调节自分泌IGF-I介导生长的机制。
