ERK1/2 mediates the lipopolysaccharide-induced upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in cardiac fibroblasts

被引：20

作者：

Chen, Liang-Chi ^{[1
]}

Shibu, Marthandam Asokan ^{[2
]}

Liu, Chung-Jung ^{[3
]}

Han, Chien-Kuo ^{[4
]}

Ju, Da-Tong ^{[5
]}

Chen, Pei-Yu ^{[1
]}

Viswanadha, Vijaya Padma ^{[6
]}

Lai, Chao-Hung ^{[7
]}

Kuo, Wei-Wen ^{[8
]}

Huang, Chih-Yang ^{[4
,9
,10
]}

机构：

[1] China Med Univ Hosp, Dept Pathol, Taichung, Taiwan

[2] China Med Univ & Hosp, Med Res Ctr Exosome & Mitochondria Related Dis, Taichung, Taiwan

[3] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Gastroenterol, Kaohsiung, Taiwan

[4] Asia Univ, Dept Biotechnol, Taichung, Taiwan

[5] Natl Def Med Ctr, Triserv Gen Hosp, Dept Neurol Surg, Taipei, Taiwan

[6] Bharathiar Univ, Dept Biotechnol, Coimbatore 641046, Tamil Nadu, India

[7] Taichung Armed Force Gen Hosp, Dept Internal Med, Div Cardiol, Taichung, Taiwan

[8] China Med Univ, Dept Biol Sci & Technol, Taichung, Taiwan

[9] Tzu Chi Univ, Hualien Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Coll Med, Hualien, Taiwan

[10] China Med Univ, Grad Inst Basic Med Sci, Taichung, Taiwan

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2019年 / 306卷

关键词：

Lipopolysaccharide; Cardiac fibroblast; uPA; MMPs; Cellular migration; TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-KINASES; CHRONIC HEART-FAILURE; MATRIX METALLOPROTEINASES; OXIDATIVE STRESS; DILATED CARDIOMYOPATHY; INDUCED INFLAMMATION; TARGETED DELETION; TRANSGENIC MICE; RENAL FIBROSIS;

D O I：

10.1016/j.cbi.2019.04.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Myocardial fibrosis is a critical event during septic shock. Upregulation in the fibrosis signaling cascade proteins such as fibroblast growth factor (FGF), urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and activation of matrix metalloproteinases (MMPs) are widely associated with the development of myocardial infarction, dilated cardiomyopathy, cardiac fibrosis and heart failure. However, evidences suggest that the common upstream mediators of fibrosis cascade play little role in cardiac fibrosis induced by LPS; further, it is unknown if LPS directly triggers the expressions and/or activity of FGF-2, uPA, tPA, MMP-2 and MMP-9 in cardiac fibroblasts. In the present study, we treated primary cultures of cardiac fibroblasts with LPS to explore whether LPS upregulates FGF-2, uPA, tPA, MMP-2, MMP-9 and enhance cellular migration. Further the precise molecular and cellular mechanisms behind these LPS induced responses were identified. Inhibition assays on MAPKs using U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin inhibitor) and QNZ (NF kappa B inhibitor) show that LPS-induced upregulation of FGF-2, uPA, MMP-2 and MMP-9 in cardiac fibroblasts was mediated through ERK1/2 signaling. Collectively, our results provide a link between LPS-induced cardiac dysfunction and ERK1/2 signaling pathway and thereby implies ERK1/2 as a possible target to regulate LPS induced upregulation of FGF-2, uPA, MMP-2, MMP-9 and cellular migration in cardiac fibroblasts.

引用

页码：62 / 69

页数：8