The Journal of Nutrition Vol. 127 No. 7 July 1997, pp. 1297-1303
Copyright ©1997 by the American Society for Nutritional Sciences

Retinoic Acid Stimulates Early Cellular Proliferation in the Adapting Remnant Rat Small Intestine after Partial Resection

Manuscript received 30 July 1996. Initial reviews completed 30 August 1996. Revision accepted 7 March 1997.

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110

Following loss of small bowel surface area, the remnant intestine undergoes a remarkable adaptive response. To define more fully the underlying molecular mechanisms, we have identified genes that are specifically induced in the adapting remnant after partial small bowel resection. Several of these, including cellular retinol binding protein II (CRBP II) and apolipoprotein (apo) AI, participate in vitamin A and lipid trafficking. The CRBP II and apo A-I promoters contain response elements for the nuclear retinoid X receptor RXR-. It is well established that vitamin A is essential for normal cell growth, differentiation and maintenance of epithelial tissues and that CRBP II functions to facilitate intestinal vitamin A absorption and metabolism. On the basis of these considerations, changes in CRBP II and apo A-I mRNA levels could reflect a role for retinoids in modulating the intestinal adaptive 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- expression postresection. CRBP II and apo A-I mRNA levels were increased in the remnant intestine in distinct temporal patterns, whereas RXR- expression was unchanged. To address directly the effects of vitamin A in adaptation, retinoic acid or vehicle was administered intravenously to rats immediately after 70% small bowel resection. Compared with vehicle, all-trans-retinoic acid significantly stimulated crypt cell proliferation in the adapting remnant intestine by 6 h after surgery. These data suggest that retinoic acid acts to modulate intestinal proliferation in the adapting small intestine after loss of functional small bowel surface area.

Key words: intestinal adaptation, retinoids, cellular retinol binding protein II, apolipoprotein AI rats.

This article has been cited by other articles:

				L. Wang, Y. Tang, D. C. Rubin, and M. S. Levin Chronically administered retinoic acid has trophic effects in the rat small intestine and promotes adaptation in a resection model of short bowel syndrome Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1559 - G1569. [Abstract] [Full Text] [PDF]

				T. H. Tezel, L. Geng, H. J. Kaplan, and L. V. Del Priore Retinal Pigment Epithelium Rescues Vascular Endothelium from Retinoic Acid-Induced Apoptosis Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5075 - 5087. [Abstract] [Full Text] [PDF]

				D. A. Swartz-Basile, L. Wang, Y. Tang, H. A. Pitt, D. C. Rubin, and M. S. Levin Vitamin A deficiency inhibits intestinal adaptation by modulating apoptosis, proliferation, and enterocyte migration Am J Physiol Gastrointest Liver Physiol, July 7, 2003; 285(2): G424 - G432. [Abstract] [Full Text] [PDF]

				X. E, L. Zhang, J. Lu, P. Tso, W. S. Blaner, M. S. Levin, and E. Li Increased Neonatal Mortality in Mice Lacking Cellular Retinol-binding Protein II J. Biol. Chem., September 20, 2002; 277(39): 36617 - 36623. [Abstract] [Full Text] [PDF]

				D. C. Rubin, E. A. Swietlicki, H. Iordanov, C. Fritsch, and M. S. Levin Novel goblet cell gene related to IgGFcgamma BP is regulated in adapting gut after small bowel resection Am J Physiol Gastrointest Liver Physiol, November 1, 2000; 279(5): G1003 - G1010. [Abstract] [Full Text] [PDF]

				D. C. Rubin, E. A. Swietlicki, J. L. Wang, and M. S. Levin Regulation of PC4/TIS7 expression in adapting remnant intestine after resection Am J Physiol Gastrointest Liver Physiol, September 1, 1998; 275(3): G506 - G513. [Abstract] [Full Text] [PDF]

				A. Goyal, R. Singh, E. A. Swietlicki, M. S. Levin, and D. C. Rubin Characterization of rat epimorphin/syntaxin 2 expression suggests a role in crypt-villus morphogenesis Am J Physiol Gastrointest Liver Physiol, July 1, 1998; 275(1): G114 - G124. [Abstract] [Full Text] [PDF]