Hodin R A, Graham J R, Meng S, Upton M P
Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Am J Physiol. 1994 Jan;266(1 Pt 1):G83-9. doi: 10.1152/ajpgi.1994.266.1.G83.
Studies were carried out to elucidate the molecular mechanisms underlying small intestinal epithelial growth. Adult rats were fasted for 4 days and then refed a chow diet for up to 48 h. Histological examination confirmed the sequential occurrence of mucosal atrophy and hyperplasia. Northern blot analyses of RNA derived from small intestinal mucosal scrapings revealed a striking pattern of alterations in the expression of two different categories of genes. There were very early increases in the expression of c-fos and c-jun, reflecting the mitogenic response to refeeding that occurs within the crypt compartment. Studies using the protein synthesis inhibitor cycloheximide suggest that c-fos and c-jun are part of the "immediate-early" response of the small intestine. At later time points after the refeeding stimulus, differential changes occurred in the expression of the brush-border enzymes, lactase, and intestinal alkaline phosphatase (IAP). Refeeding caused a decrease in lactase gene expression and an increase in the expression of the 3.0-kb IAP mRNA species, reflecting a return of the villus phenotype to the normal fed state. Thus we have demonstrated a complex and temporally related pattern of gene expression within the small intestinal epithelium upon refeeding. The results provide insight into the relationship between the processes of intestinal growth and differentiation.
开展了多项研究以阐明小肠上皮生长的分子机制。成年大鼠禁食4天，然后再喂普通饲料长达48小时。组织学检查证实了黏膜萎缩和增生的相继发生。对从小肠黏膜刮片中提取的RNA进行Northern印迹分析，揭示了两类不同基因表达的显著变化模式。c-fos和c-jun的表达非常早期就增加了，这反映了隐窝区对再喂养产生的促有丝分裂反应。使用蛋白质合成抑制剂环己酰亚胺的研究表明，c-fos和c-jun是小肠“即刻早期”反应的一部分。在再喂养刺激后的后期时间点，刷状缘酶、乳糖酶和肠碱性磷酸酶（IAP）的表达发生了差异变化。再喂养导致乳糖酶基因表达下降，3.0-kb IAP mRNA种类的表达增加，这反映了绒毛表型恢复到正常进食状态。因此，我们证明了再喂养后小肠上皮内基因表达存在复杂且与时间相关的模式。这些结果为深入了解肠道生长和分化过程之间的关系提供了线索。
