RETINOIC ACID STIMULATES EARLY CELLULAR PROLIFERATION IN THE ADAPTINGREMNANT RAT SMALL-INTESTINE AFTER PARTIAL RESECTION

Following loss of small bowel surface area, the remnant intestine unde rgoes a remarkable adaptive response, To define more fully the underly ing molecular mechanisms, we have identified genes that are specifical ly induced in the adapting remnant after partial small bowel resection . Several of these, including cellular retinol binding protein II (CRB P II) and apolipoprotein (apo) Al, participate in vitamin A and lipid trafficking. The CRBP II and apo A-I promoters contain response elemen ts for the nuclear retinoid X receptor RXR-alpha. It is well establish ed that vitamin A is essential for normal cell growth, differentiation and maintenance of epithelial tissues and that CRBP II functions to f acilitate intestinal vitamin A absorption and metabolism, On the basis of these considerations, changes in CRBP II and apo A-I mRNA levels c ould reflect a role for retinoids in modulating the intestinal adaptiv e response, To explore this hypothesis, we used a rat resection model of intestinal adaptation to examine the temporal patterns of CRBP II, apo A-I and RXR-alpha expression postresection, CRBP II and apo A-I mR NA levels were increased in the remnant intestine in distinct temporal patterns, whereas RXR-alpha expression was unchanged. To address dire ctly the effects of vitamin A in adaptation, retinoic acid or vehicle was administered intravenously to rats immediately after 70% small bow er resection. Compared with vehicle, all-trans-retinoic acid significa ntly stimulated crypt cell proliferation in the adapting remnant intes tine by 6 h after surgery, These data suggest that retinoic acid acts to modulate intestinal proliferation in the adapting small intestine a fter loss of functional small bowel surface area.