Majumdar A P, Luk G D
Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan.
J Clin Gastroenterol. 1992;14 Suppl 1:S25-8. doi: 10.1097/00004836-199206001-00004.
The mucosa of the gastrointestinal tract, including the stomach, undergoes constant renewal. The gastric mucosa is able to regenerate after injury, and this regeneration is associated with increases in epithelial cell proliferation. Gastric epithelial regeneration has been suggested to be impaired with aging. Using a hyperosmolar injury model, we found that gastric epithelial proliferation was markedly lower in aged rats. To elucidate further the regulation of gastric epithelial proliferation after injury, we studied the induction of ornithine decarboxylase and tyrosine kinase. Ornithine decarboxylase is the first and often rate-limiting enzyme in polyamine biosynthesis and tyrosine kinase catalyzes phosphorylation of protein tyrosine residues, and both enzymes have been implicated as important in cell proliferation. We found that hyperosmolar injury induction of ornithine decarboxylase and tyrosine kinase was markedly lower in aged rats. Furthermore, inhibition of ornithine decarboxylase or of tyrosine kinase greatly suppressed gastric epithelial proliferation. Our results confirm that ornithine decarboxylase and tyrosine kinase are important in gastric epithelial proliferation. Further studies of these two enzyme pathways may help elucidate the regulation of gastric epithelial growth and regeneration, particularly the potential alterations with aging.
胃肠道黏膜，包括胃黏膜，会持续更新。胃黏膜在损伤后能够再生，这种再生与上皮细胞增殖增加有关。有研究表明，胃上皮再生会随着衰老而受损。我们使用高渗损伤模型发现，老年大鼠的胃上皮增殖明显较低。为了进一步阐明损伤后胃上皮增殖的调控机制，我们研究了鸟氨酸脱羧酶和酪氨酸激酶的诱导情况。鸟氨酸脱羧酶是多胺生物合成中的首个且通常是限速酶，酪氨酸激酶催化蛋白质酪氨酸残基的磷酸化，这两种酶都被认为在细胞增殖中起重要作用。我们发现，老年大鼠中高渗损伤诱导的鸟氨酸脱羧酶和酪氨酸激酶明显较低。此外，抑制鸟氨酸脱羧酶或酪氨酸激酶会极大地抑制胃上皮增殖。我们的结果证实，鸟氨酸脱羧酶和酪氨酸激酶在胃上皮增殖中起重要作用。对这两条酶途径的进一步研究可能有助于阐明胃上皮生长和再生的调控机制，特别是衰老可能带来的潜在变化。
