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机制 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。调查人员提出以下建议 级联发生在亨利氏袢髓质厚升肢 (mTAL)：AII 诱导肿瘤坏死因子-α (TNF)，进而诱导 COX-2 基因 表达，导致 PGE2 的产生。钠的重吸收 mTAL 被 PGE2 抑制，从而导致尿钠排泄。具体目标 该项目是 1) 确定 AII 增加 COX-2 的机制 mTAL 和其他肾单位段中的表达，以及 2) 评估 内源性皮质类固醇和 TAL 表型对肾脏 COX-2 的调节 并表征含有 COX-2 的细胞。这些具体目标是一个延伸 家长补助金的具体目标。美国调查人员将使用 外国研究者将使用的细胞和分子方案 体内模型、免疫组织化学和原位杂交技术 调查具体目标。