Neuroendocrine regulation of expression of apolipoprotein A-IV gene in intestinal epithelial cells

本研究探讨了神经和内分泌因素在肠上皮细胞载脂蛋白A-IV（A-IV）基因表达调控中的作用。静脉注射神经节阻滞剂、胆碱能拮抗剂和NOS抑制剂可抑制大鼠回肠A-IV mRNA的表达，提示A-IV基因受胆碱能和NO能神经元的调节。A-TV mRNA不受β-肾上腺素能、多巴胺能、肾上腺素能、ATR能拮抗剂的影响。由于神经节阻滞剂不能抑制饮食脂质和大面积小肠切除后适应性回肠中A-IV mRNA水平的增加，因此上调不太可能与神经有关。在Caco-2肠细胞中，PYY以时间和剂量依赖性方式上调A-IV基因。VIP、蛙皮素和P物质也增加A-IV mRNA，而生长抑素28抑制它，肾上腺素、卡巴胆碱、胰高血糖素、GRP、NPY、CGRP、GLP和Met-脑啡肽没有影响。这些结果表明，A-IV基因在肠上皮细胞中的表达受到许多与肠道激素和神经肽相关的因素的调节。

The present study investigated the role of neural and endocrine factors in the regulation of expression of apolipoprotein A-IV (A-IV) gene in intestinal epithelial cells. Intravenous infusion of ganglionic blocker, cholinergic antagonist, and NOS inhibitor suppressed the expression of A-IV mRNA in rat ileum, suggesting regulation of A-IV gene by cholinergic and NOergic neurons. A-TV mRNA was not affected byβ-adrenergic, dopaminergic, serotonergic, ATRergic antagonists. Since ganglionic blocker did not suppress the increase in A-IV mRNA level by dietary lipid and in adaptive ileum after massive small bowel resection, the upregulation is unlikely to be associated with nerve. In Caco-2 intestinal cells, PYY upregulated the A-IV gene in time-and dose-dependent manner. VIP, bombesin, and substance P also increased the A-IV mRNA, while somatostatin28 suppressed it and, adrenaline, carbachol, glucagon, GRP, NPY, CGRP, GLP, and Met-enkephaline had no effect. These results suggest that expression of A-IV gene in intestinal epithelial cells is regulated by a number of factors associated with gut hormones and neural peptides.