Hodin R A, Meng S, Shei A
Department of Surgery, Beth Israel Hospital, Harvard Medical School, Harvard Digestive Diseases Center, Boston, MA 02215.
Surgery. 1994 Aug;116(2):426-31.
Previous studies have suggested a relationship between enterocyte phenotype and the growth state of the epithelium; under atrophic conditions, lactase gene expression is high, whereas intestinal alkaline phosphatase (IAP) expression is low, and vice versa. On the basis of this model, we hypothesized that the intestinal trophic factor bombesin would alter brush-border enzyme gene expression in a predictable way.
Adult rats were fasted for 48 hours and treated (intraperitoneally) with either 10 micrograms/kg bombesin or the saline control every 8 hours. Small intestinal mucosal scrapings were taken, total RNA purified, and Northern blot analyses performed with radiolabeled cDNA probes corresponding to lactase, IAP, villin, and actin. Tissue samples were also taken for measurement of mucosal thickness.
Bombesin administration caused an increase in jejunal mucosal thickness, thereby confirming its trophic effects. Bombesin resulted in a decrease in lactase mRNA levels and an increase in IAP mRNA levels along the length of the small intestine. No changes occurred in the expression of either villin or actin. The pattern of enterocyte gene expression in the bombesin-treated animals was similar to that in control-fed rats.
Bombesin differentially regulates rat enterocyte gene expression, decreasing lactase and increasing IAP mRNA levels. These results lend further support to the hypothesis that a close relationship exists between enterocyte phenotype and epithelial growth state.
先前的研究表明肠上皮细胞表型与上皮生长状态之间存在关联；在萎缩状态下，乳糖酶基因表达较高，而肠碱性磷酸酶（IAP）表达较低，反之亦然。基于此模型，我们推测肠营养因子蛙皮素会以可预测的方式改变刷状缘酶基因的表达。
成年大鼠禁食48小时，每8小时腹腔注射10微克/千克蛙皮素或生理盐水对照。取小肠黏膜刮片，纯化总RNA，并用与乳糖酶、IAP、绒毛蛋白和肌动蛋白相对应的放射性标记cDNA探针进行Northern印迹分析。还取组织样本测量黏膜厚度。
给予蛙皮素导致空肠黏膜厚度增加，从而证实了其营养作用。蛙皮素导致小肠全长乳糖酶mRNA水平降低，IAP mRNA水平升高。绒毛蛋白或肌动蛋白的表达均未发生变化。经蛙皮素处理的动物中肠上皮细胞基因表达模式与对照喂养大鼠相似。
蛙皮素差异性调节大鼠肠上皮细胞基因表达，降低乳糖酶水平并增加IAP mRNA水平。这些结果进一步支持了肠上皮细胞表型与上皮生长状态之间存在密切关系的假说。
