Williams Kristen L, Fuller C Randall, Fagin James, Lund P Kay
Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599-7080, USA.
Am J Physiol Gastrointest Liver Physiol. 2002 Oct;283(4):G875-85. doi: 10.1152/ajpgi.00089.2002.
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 (TG) mice 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 mice 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.
在肠道上皮适应性生长过程中，局部胰岛素样生长因子-I（IGF-I）在肠道间充质中的表达常常增加，但IGF-I在体内的旁分泌生长作用尚未明确。我们测试了肠道间充质中IGF-I的过表达是否会增加上皮生长，以及其作用是否与循环IGF-I的已知作用不同。SMP8-IGF-I转基因（TG）小鼠在α-平滑肌肌动蛋白启动子的驱动下过表达IGF-I。评估了SMP8-IGF-I-TG小鼠和野生型同窝小鼠空肠、回肠和结肠的黏膜和肌层生长情况。测定了SMP8-IGF-I转基因以及IGF结合蛋白（IGFBP）-3和-5 mRNA的丰度。SMP8-IGF-I-TG小鼠的回肠黏膜生长增加，但空肠或结肠未增加；整个肠道的肌层生长均增加。SMP8-IGF-I-TG小鼠空肠和回肠中的IGFBP-5 mRNA增加，且在回肠固有层中特异性上调。肠道间充质细胞中IGF-I的过表达对回肠黏膜上皮具有优先旁分泌作用，对整个肠道的肌层具有自分泌作用。与循环IGF-I相比，局部表达的IGF-I对IGFBP表达具有不同的作用。
