Abstract
Adenine nucleotides have been demonstrated to enhance structural and functional regeneration in experimental renal injury in rats. The mechanism of adenine nucleotide action have not been elucidated. The aim of this study was to characterize the effects of adenine nucleotides on intestinal epithelial wound healing in vitro. The effects of adenine nucleotides on cell migration, cell proliferation and cell adhesion were studied in the non-transformed small intestinal epithelial cell line IEC-6 using an in vitro wounding model, a colorimetric BrdU assay and a hexosaminidase adhesion assay. The adenine nucleotides ADP and ATP were found to significantly stimulate epithelial cell restitution (migration) in vitro. Stimulation of epithelial restitution averaged 42% for ADP and 57% for ATP. In addition, adenine nucleotides inhibited the proliferation of rat small intestinal epithelial cells, averaging 56% for ADP and 74% for ATP. Enhancement of intestinal epithelial restitution and inhibition of epithelial cell proliferation by adenine nucleotides were mediated through transforming growth factor (TGF)-beta-independent pathways. These findings suggest that adenine nucleotides exert functional effects on intestinal epithelial cell populations and may play a role in the morphogenesis of the gastrointestinal tract and its remodeling after injury.
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