ABSTRACT
Treatment with transforming growth factor-beta(1) (TGF-beta(1)) has been shown to be effective in accelerating skin wound healing. Another approach to gain the beneficial effects of TGF-beta(1) on wound healing could be the activation of tissue stores of latent TGF-beta(1) with agents such as vitamin A. The aims of this study were to determine whether 1) vitamin A is effective in enhancing intestinal wound healing in vitro and 2) activation of TGF-beta(1) is increased during wound healing with vitamin A treatment. We used the intraluminal chemical induction model of necrotizing enterocolitis (NEC), which was adapted to the 1-wk-old piglet. Injured (NEC) and noninjured full-thickness ileum explants harvested from the piglets were cultured for 24 and 48 h in serum-free medium supplemented with all-trans retinol (ATR; 0, 2, 5, and 10 microM). All concentrations of ATR improved recovery of normal ileal wall cytoarchitecture of NEC explants, with maximal recovery observed with 2 microM ATR after 24 h of culture. Further recovery after 48 h was observed with 5 and 10 microM ATR but did not achieve the degree of healing observed with 2 microM ATR. There were no observable adverse effects of ATR on noninjured ileal explant morphology. Active TGF-beta(1) was identified only in the NEC explants incubated with ATR. The results of this study demonstrate that administration of vitamin A accelerates recovery of normal intestinal wall cytoarchitecture of injured ileum in vitro, without adversely affecting noninjured ileum. The increased activation of latent TGF-beta(1) may, in part, be responsible for the accelerated healing of injured ileum observed with vitamin A administration.
