REGULATION OF RENAL CYCLOOXYGENASE-2

应用程序的目的是确定 血管紧张素II（AII）和内源性糖皮质激素调节 肾脏中的环氧合酶-2调查人员建议， 级联发生在髓厚汉勒袢升支（mTAL）：AII 诱导肿瘤坏死因子-α（TNF），其又诱导考克斯-2基因 表达导致PGE 2的产生。脑中的钠重吸收 mTAL被PGE 2抑制，从而导致尿钠排泄。的具体目标 该项目是1）确定AII增加考克斯-2的机制 mTAL和其他肾单位片段中的表达，以及2）评估 内源性皮质类固醇对肾脏考克斯-2的调节与TAL表型 并表征含有考克斯-2的细胞。这些具体目标是一种延伸， 父母补助金的具体目的。美国调查人员将使用 细胞和分子方案，而外国研究人员将使用在 体内模型，免疫组织化学和原位杂交技术， 研究具体目标。

The purpose of the application is to determine the mechanisms by which angiotensin II (AII) and endogenous glucocorticoids regulate expression of cyclooxygenase-2 in the kidney. The investigators propose that the following cascade occurs in medullary thick ascending limb of Henle's loop (mTAL): AII induces tumor necrosis factor-alpha (TNF) which in turn induces COX-2 gene expression which results in the production of PGE2. Sodium reabsorption in the mTAL is inhibited by PGE2 thus resulting in natriuresis. The specific aims of the project are 1) to determine the mechanism(s) by which AII increases COX-2 expression in the mTAL and other nephron segments, and 2) to assess the regulation of renal COX-2 by endogenous corticosteroids and phenotype of TAL and characterize cells that contain COX-2. These specific aims are an extension of the specific aims of the parent grant. The U.S. investigator will use cellular and molecular protocols while the foreign investigator will use in vivo models, immunohistochemical and in situ hybridization techniques to investigate the specific aims.