Cross talk of tumor necrosis factor-α and the renin-angiotensin system in tumor necrosis factor-α-induced plasminogen activator inhibitor-1 production from hepatocytes

被引：27

作者：

Takeshita, Yurnie ^{[1
]}

Takamura, Toshinari ^{[1
]}

Ando, Hitoshi ^{[1
]}

Hamaguchi, Erika ^{[1
]}

Takazakura, Akiko ^{[1
]}

Matsuzawa-Nagata, Naoto ^{[1
]}

Kaneko, Shuichi ^{[1
]}

机构：

[1] Kanazawa Univ, Grad Sch Med Sci, Dept Dis Control & Homeostasis, Kanazawa, Ishikawa 9208641, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2008年 / 579卷 / 1-3期

关键词：

tumor necrosis factor-alpha; renin-angiotensin system; plasminogen activator inhibitor-1; liver; angiotensin type 1 receptor;

D O I：

10.1016/j.ejphar.2007.11.016

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Tumor necrosis factor (TNF)-alpha and local activation of the renin-angiotensin system may contribute to insulin resistance and atherosclerosis. In this study, we investigated the involvement of these mediators in the liver. We found that the gene expression of renin-angiotensin system components, together with that of plasminogen activator inhibitor (PAI)-1, is upregulated in the liver of patients with obesity and type 2 diabetes. We next examined the role of the renin-angiotensin system on TNF-alpha-induced PAI-1 production in the nonmalignant human hepatocyte cell line THLE-5b. THLE-5b cells expressed genes encoding renin-angiotensin system components including angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin type 1(AT(1))receptor. ACE, angiotensinogen, and angiotensin AT, receptor mRNA expression were upregulated time-dependently by TNF-alpha. Moreover, angiotensin AT, receptor antagonist dose-dependently inhibited TNF-alpha-induced PAI-1 production. Interestingly, high-dose olmesartan, but not candesartan, reduced the increased expression of the angiotensin AT, receptor. These results suggest that TNF-alpha. and the local renin-angiotensin system coordinately stimulate PAI-1 production in hepatocytes. Selective angiotensin AT, receptor antagonists inhibit both TNF-alpha- and angiotensin II-induced PAI-1 production in hepatocytes., suggesting a cross talk between both systems. (c) 2007 Elsevier B.V. All rights reserved.

引用

页码：426 / 432

页数：7

共 36 条

[1] Transcription factor decoy for activator protein-1 (AP-1) inhibits high glucose- and angiotensin II-induced type 1 plasminogen activator inhibitor (PAI-1) gene expression in cultured human vascular smooth muscle cells [J].