Rubin D C, Swietlicki E A, Wang J L, Levin M S
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Physiol. 1998 Sep;275(3):G506-13. doi: 10.1152/ajpgi.1998.275.3.G506.
The adaptive response of the small intestine to loss of functional surface area includes enhanced crypt cell proliferation and enterocyte differentiation. To better define the underlying molecular and cellular mechanisms, we have cloned rat genes that are specifically regulated in the adaptive gut after 70% small intestinal resection. One of these is the immediate early gene PC4/TIS7. Compared with sham-resected control ileum, PC4/TIS7 mRNA levels in the adaptive remnant ileum were markedly increased at 16 and 48 h but not 1 wk after resection. Greater augmentation of PC4/TIS7 mRNA levels occurred in the ileum compared with the duodenum and proximal jejunum. After resection, the changes in intestinal PC4/TIS7 mRNA levels also exceeded changes in extraintestinal levels. The demonstration by in situ hybridization that villus-associated, but not crypt, cells express PC4/TIS7 mRNA is consistent with a role in regulating cytodifferentiation. The pattern of expression in the Caco-2 cell line is also consistent with such a role. Although the precise function of PC4/TIS7 in adaptation remains unclear, the early and intestine-specific changes in mRNA levels after 70% resection suggest that it might augment the adaptive response by stimulating the production of differentiated enterocytes.
小肠对功能性表面积丧失的适应性反应包括隐窝细胞增殖增强和肠上皮细胞分化。为了更好地确定潜在的分子和细胞机制，我们克隆了大鼠基因，这些基因在70%小肠切除术后的适应性肠道中受到特异性调节。其中之一是即早基因PC4/TIS7。与假手术切除的对照回肠相比，适应性残余回肠中PC4/TIS7 mRNA水平在切除后16小时和48小时显著升高，但在1周后未升高。与十二指肠和空肠近端相比，回肠中PC4/TIS7 mRNA水平的升高幅度更大。切除后，肠道PC4/TIS7 mRNA水平的变化也超过了肠外水平的变化。原位杂交显示绒毛相关细胞而非隐窝细胞表达PC4/TIS7 mRNA，这与调节细胞分化的作用一致。Caco-2细胞系中的表达模式也与此作用一致。尽管PC4/TIS7在适应性反应中的精确功能仍不清楚，但70%切除术后mRNA水平的早期和肠道特异性变化表明，它可能通过刺激分化肠上皮细胞的产生来增强适应性反应。
