REGULATION OF UROGUANYLIN BY DIETARY ZINC STATUS

这项修订后的申请建议延长对这些问题的观察 研究人员认为多肽激素尿鸟苷的前体mRNA 因缺锌而上调。尿鸟苷是一种肠道 其受体鸟苷环化酶-C起重要作用的激素 在调节肠道液体平衡方面的作用。有文献报道说 补充锌可以纠正分泌性腹泻，从而与 尿鸟苷缺锌。这个项目的目标是 描述锌中毒时尿鸟苷诱导的真实原因 并确定这是否可以提供 补锌逆转骨质疏松症临床症状的机制 分泌性腹泻。修订后的提案中有六个具体目标 已列出。1)锌对尿鸟苷基因表达调控的时程 不足之处将被确定。2)锌对尿鸟苷基因表达的调节 将以回收为特征。3)采用原位杂交技术 确定哪些细胞类型表达尿鸟苷前体。4)使用 最近制备的抗体，尿鸟苷前体的水平将 与尿鸟苷基因的表达水平有关。5)使用原位结扎环， 饮食不足对肠液分泌的影响将是 已评估。6)研究人员提议开始对T-84细胞的研究 或Caco-2细胞，以测试介质锌浓度对 尿鸟苷前体mRNA和/或多肽水平。

This revised application proposes to extend the observation of these researchers that the precursor mRNA for the peptide hormone uroguanylin is up-regulated by zinc deficiency. Uroguanylin is an intestinal hormone whose receptor, guanylate cyclase-C, plays a significant role in regulating intestinal fluid balance. Literature reports that supplemental zinc can correct secretory diarrhea and thus links uroguanylin with zinc deficiency. The objective of this project is to characterize the true causes of uroguanylin induction during zinc deficiency in rats, and to determine whether this could provide the mechanism by which Zn supplementation reverses the clinical sides of secretory diarrhea. Six specific aims in the revised proposal are listed. 1) The time course of uroguanylin mRNA regulation by zinc during deficiency will be determined. 2) Uroguanylin mRNA regulation by zinc repletion will be characterized. 3) In situ hybridization will be used to determine which cell types express uroguanylin precursor. 4) Using recently prepared antibodies, levels of uroguanylin precursor will be related to levels of uroguanylin mRNA. 5) Using in situ ligated loops, the effect of dietary deficiency on intestinal fluid secretion will be evaluated. 6) The researchers proposed to begin studies with T-84 cells or Caco-2 cells to test the impact of media zinc concentration on uroguanylin precursor mRNA and/or peptide levels.