ENTEROCYTIC GENE-EXPRESSION IN INTESTINAL ADAPTATION - EVIDENCE FOR ASPECIFIC CELLULAR-RESPONSE

After massive small bowel resection, the remnant gut epithelium underg oes an adaptive response marked by an increase in villus height, crypt depth, and crypt cell production rate. Although morphological feature s of gut adaptation have been well characterized, the differentiation status and response of epithelial cells populating the adaptive villus is unclear. To address these issues, cell-specific and spatial patter ns of expression of a set of enterocytic genes were characterized in r ats after 70% small bowel resection. The liver and intestinal (I) fatt y acid binding protein (FABP) and apolipoprotein A-I (ape A-I) and apo A-IV genes were studied because they exhibit unique regional and cell -specific patterns of expression in the developing and adult gut. At 4 8 h after surgery, apo A-IV and I-FABP mRNA levels were increased up t o 3.5-fold in adaptive remnant ileum compared with sham-operated or sh am-resected control ileum. In situ hybridization and immunohistochemic al analyses revealed a marked increase in enterocytic apo A-TV mRNA an d protein expression in the adaptive ileum, from villus base to tip bu t not in crypts. By 1 wk after resection, apo A-TV, but not I-FABP, mR NA levels remained elevated in remnant ileum, although duodenal I-FABP mRNA levels were still increased. In contrast, apo A-I mRNA levels we re not significantly induced. These results indicate that the enterocy te can respond acutely to loss of small bowel surface area by increasi ng expression of several genes. This compensatory enterocytic response is spatially (from duodenum to ileum) and temporally regulated. These results suggest initiation of the adaptive response occurs by way of a complex set of molecular pathways involving villus and crypt cells.