REGULATION OF PC4 TIS7 EXPRESSION IN ADAPTING REMNANT INTESTINE AFTERRESECTION/

The adaptive response of the small intestine to loss of functional sur face area includes enhanced crypt cell proliferation and enterocyte di fferentiation. To better define the underlying molecular and cellular mechanisms, we have cloned rat genes that are specifically regulated i n the adaptive gut after 70% small intestinal resection. One of these is the immediate early gene PC4/TIS7. Compared with sham-resected cont rol ileum, PC4/TIS7 mRNA levels in the adaptive remnant ileum were mar kedly increased at 16 and 48 h but not 1 wk after resection. Greater a ugmentation of PC4/TIS7 mRNA levels occurred in the ileum compared wit h the duodenum and proximal jejunum. After resection, the changes in i ntestinal PC4/TIS7 mRNA levels also exceeded changes in extraintestina l levels. The demonstration by in situ hybridization that villus-assoc iated, 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 sug gest that it might augment the adaptive response by stimulating the pr oduction of differentiated enterocytes.