Adiponectin Inhibits TNF-α-Activated PAI-1 Expression Via the cAMP-PKA-AMPK-NF-κB Axis in Human Umbilical Vein Endothelial Cells

被引：31

作者：

Chen, Yijian ^{[1
]}

Zheng, Yongliang ^{[2
]}

Liv, Liping ^{[1
]}

Lin, Chuanming ^{[1
]}

Liao, Changfeng ^{[1
]}

Xin, Liuyan ^{[1
]}

Zhong, Sisi ^{[1
]}

Cheng, Qilai ^{[3
]}

Zhang, Liqun ^{[4
]}

机构：

[1] Gannan Med Univ, Affiliated Hosp 1, Hematol Dept, Ganzhou, Jiangxi, Peoples R China

[2] Jinggangshan Univ, Affiliated Hosp, Hematol Dept, Jian, Jiangxi, Peoples R China

[3] Gannan Med Univ, Coll Pharm, Ganzhou 341000, Jiangxi, Peoples R China

[4] Gannan Med Univ, Affiliated Hosp 1, Qual Control Dept, Ganzhou 341000, Jiangxi, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2017年 / 42卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Antifibrotic effect; Binding capability; Promoter; Plasminogen activator inhibitor; Adiponectin; TUMOR-NECROSIS-FACTOR; PLASMA-PROTEIN; TGF-BETA; PATHOGENESIS;

D O I：

10.1159/000480006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background: Tumor necrosis factor (TNF)-alpha can upregulate the expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of fibrinolysis. Adiponectin (Adp) antagonizes TNF-alpha by negatively regulating its expression in various tissues. In the present study, the ability of Adp to suppress TNF-alpha-induced PAI-1 upregulation and the underlying mechanisms were evaluated. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with TNF-alpha in the presence or absence of Adp, and PAI-1 mRNA and antigen expression, activated signaling pathways, and molecular mechanisms were analyzed by qRT-PCR and ELISA. Results: Adp decreased the TNF-alpha-induced upregulation of PAI-1 mRNA and protein expression and suppressed TNF-alpha-induced cAMP-PKA-AMPK inactivation. Adp also suppressed the TNF-alpha-induced NE-kappa B binding capability on the PAI-1 promoter. Moreover, these Adp-induced effects were further enhanced or prevented by treatment with the cAMP inhibitor Rp-cAMPs or activator forskolin, respectively. Conclusions: Our data suggest that Adp abrogates TNF-alpha-activated PAI-1 expression by activating cAMP-PKA-AMPK signaling to suppress NE-kappa B binding to the PAI-1 promoter in HUVECs. Given the antifibrotic effect of PAI-1 abrogation, Adp may be utilized as a novel agent in the treatment of fibrotic diseases. (C) 2017 The Author(s) Published by S. Karger AG, Basel

引用

页码：2342 / 2352

页数：11

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