Enhanced growth of small bowel in transgenic mice expressing human insulin-like growth factor I
Enhanced growth of small bowel in transgenic mice expressing human insulin-like growth factor I
复制标题
DOI：
10.1053/gast.1997.v112.pm9024298
复制
发表时间：
1997-02-01
期刊：
影响因子：
29.4
通讯作者：
Lund, PK
中科院分区：
文献类型：
--
作者：
Ohneda, K;Ulshen, MH;Lund, PK
背景与目的：生长激素和胰岛素样生长因子I(IGF-I)可刺激小肠生长。本研究的目的是分析IGF-I是否介导生长激素的肠道营养作用。方法：将由小鼠金属硫蛋白I启动子驱动的高表达IGF-I转基因小鼠和生长激素缺乏的转基因小鼠与野生型小鼠进行比较。检测小肠生长、IGF-I转基因信使RNA和胰岛素样生长因子结合蛋白3的丰度和定位。结果：IGF-I转基因小鼠的小肠长度和质量均大于野生型小鼠。转基因小鼠空肠绒毛高度、隐窝深度和隐窝细胞有丝分裂数均大于野生型小鼠，但空肠硬脂酸酶活性未见增加。转基因在绒毛上皮细胞中有较强的表达。胰岛素样生长因子结合蛋白3信使RNA定位于固有层。两者的区域性表达与粘膜质量的增加相关。结论：IGF-I过表达对肠道长度和粘膜质量的影响与先前观察到的生长激素过表达的影响相似。过量的IGF-I促进隐窝细胞的增殖，而过量的生长激素不会促进隐窝细胞的增殖。过量的IGF-I刺激肠上皮细胞分化的效果不如过量的生长激素。
Background & Aims: Growth hormone and insulin-like growth factor I (IGF-I) stimulate small bowel growth. The aim of this study was to analyze whether IGF-I mediates enterotrophic actions of growth hormone. Methods: IGF-I transgenic mice that overexpress an IGF-I transgene driven by the mouse metallothionein I promoter and are growth hormone deficient were compared with wild-type littermates. Growth of small bowel, abundance and localization of messenger RNAs for the IGF-I transgene, and insulin-like growth factor-binding protein 3 were assayed. Results: Small bowel length and mass were greater in IGF-I transgenic mice than in wild-type mice. Villus height, crypt depth, and crypt cell mitoses were greater in jejunum of transgenics than wild-type mice, but jejunal disacharidase activities were not increased. The transgene was expressed strongly in villus epithelial cells. Insulin-like growth factor-binding protein 3 messenger RNA was localized in the lamina propria. Regional expression of both correlated with the increase in mucosal mass. Conclusions: Effects of IGF-I overexpression on intestinal length and mucosal mass were similar to effects of growth hormone overexpression observed previously. Excess of IGF-I increased crypt cell proliferation, whereas excess of growth hormone did not increase crypt cell proliferation. IGF-I excess stimulated differentiation of intestinal epithelial cells less effectively than growth hormone excess.