REGULATION OF RENAL CYCLOOXYGENASE-2

肾环加氧酶 2 的调节

• 批准号: 6394947
• 负责人: NICHOLAS R FERRERI
• 金额: $ 3.9万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394947
• 关键词: South America; adrenalectomy; angiotensin II; angiotensin receptor; corticosteroid receptors; corticosteroids; enzyme activity; enzyme induction /repression; enzyme linked immunosorbent assay; epithelium; immunocytochemistry; kidney metabolism; laboratory rat; polymerase chain reaction; prostaglandin E; prostaglandin endoperoxide synthase; receptor expression; renal tubule; tumor necrosis factor alpha; western blottings

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.

该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的表达 肾脏中的环氧合酶-2。调查人员建议以下 级联反应发生在Henle循环（MTAL）的髓质较厚的升节中：AII 诱导肿瘤坏死因子-Alpha（TNF），进而诱导COX-2基因 表达导致PGE2产生。钠在 MTAL受到PGE2的抑制，从而导致了纳地尿。具体目的 该项目是1）确定AII增加COX-2的机制 在MTAL和其他肾单位段中的表达，2）评估 通过内源性皮质类固醇和TAL的表型调节肾脏COX-2 并表征包含COX-2的细胞。这些具体目标是扩展 父母赠款的具体目的。美国调查人员将使用 外国调查员将用于细胞和分子方案 体内模型，免疫组织化学和原位杂交技术 调查具体目标。