Evidence for a growth-stimulating fraction in the rat proximal intestine after small bowel resection

Abstract

Small bowel resection results in a compensatory hyperplasia in the small intestine, but the molecular events that lead to the increased cell production are not known. In this study, a heat-stable acidic extract of the mucosa of the proximal intestine of Sprague-Dawley rats taken 96 h after a 50% small bowel resection was capable of stimulating DNA synthesis of mouse jejunal expiants in organ culture. This stimulatory activity was present in the extracts obtained from resected animals after 48 h, 72 h, and 96 h, but was not detectable by 8 days, when presumably a new steady state was established. A significant enhancement of DNA synthesis was observed 96 h after resection when compared with groups of normal and transected animals that were pair-fed with the resected group. This activity was destroyed by protease treatment. Gel filtration experiments showed that the growth-stimulating activity present in the mucosal extract of the 96-h resected animals was due to the presence of two distinct molecules with approximate molecular weights of 4500 and 1500. The extract did not stimulate DNA synthesis in rat peripheral blood lymphocytes, mouse skin fibroblasts, and the colon adenocarcinoma cell line, HCT-8R. Similar extracts taken 96 h after resection from the distal intestine, colon, pancreas, liver, and muscle did not stimulate DNA synthesis of the mouse jejunal explants. These data suggest that the two molecules in the proximal intestine in response to resection could play a role in promoting the observed hyperplasia.