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Am J Physiol Gastrointest Liver Physiol (April 23, 2003). doi:10.1152/ajpgi.00524.2002
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Submitted on December 16, 2002
Accepted on April 14, 2003

Vitamin A Deficiency Inhibits Intestinal Adaptation by Modulating Crypt Cell Apoptosis, Proliferation and Enterocyte Migration

Deborah A. Swartz-Basile1, Lihua Wang2, Yuzhu Tang2, Henry A. Pitt3, Deborah C. Rubin2, and Marc S. Levin4*

1 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Surgery, Medical College of Wisconsin, St. Louis, MO, USA
2 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
3 Department of Surgery, Medical College of Wisconsin, St. Louis, MO, USA
4 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Specialty Care, St. Louis VA Medical Center, Milwaukee, WI, USA

* To whom correspondence should be addressed. E-mail: mlevin{at}im.wustl.edu.

In a prior study, vitamin A deficient rats subjected to submassive small bowel resections did not mount a normal intestinal adaptive response by 10 d post-operatively, although adaptive increases in crypt cell proliferation were not attenuated and there were no differences in apoptotic indices. The present study was designed to address the mechanisms by which vitamin A status effects adaptation by analyzing proliferation, apoptosis and enterocyte migration in the early post-operative period (16 h and 48 h) in vitamin A sufficient, deficient, and partially replenished sham-resected and resected rats. At 16 h post resection, apoptosis was significantly greater in the remnant ileum of resected vitamin A deficient rats compared to the sufficient controls. Crypt cell proliferation was increased by resection in all dietary groups at both timepoints. However, at 48h post resection, proliferation was significantly decreased in the vitamin A deficient and partially replenished rats. By 48 h after resection, vitamin A deficiency also reduced enterocyte migration rates by 44%. This occurred in conjunction with decreased immunoreactive collagen IV at 48 h and 10 d post-op. Laminin expression was also reduced by deficiency at 10 d post-resection, whereas fibronectin and pan-cadherin were unchanged at 48 h and 10 d. These studies indicate that vitamin A deficiency inhibits intestinal adaptation following partial small bowel resection by reducing crypt cell proliferation, by enhancing early crypt cell apoptosis and by markedly reducing enterocyte migration rates, which may be related to changes in the expression of collagen IV and other extracellular matrix components.




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