Sodium tanshinone IIA sulfonate attenuates the transforming growth factor-β1-induced differentiation of atrial fibroblasts into myofibroblasts in vitro

被引：21
作者：
Yang, Le [1 ]
Hu, Jin [2 ]
Hao, Hong-Zhen [3 ]
Yin, Zhao [3 ]
Liu, Gang [3 ]
Zou, Xiao-Jing [4 ]
机构：
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Emergency Med, Wuhan 430030, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Otolaryngol Head & Neck Surg, Wuhan 430030, Hubei, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Pharmacol, Wuhan 430030, Hubei, Peoples R China
[4] Huazhong Univ Sci & Technol, Dept Anesthesiol & Crit Care Med, Lab Anesthesiol & Crit Care Med, Union Hosp,Tongji Med Coll, Wuhan 430022, Hubei, Peoples R China
来源：
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2015年 / 35卷 / 04期
基金：
中国国家自然科学基金;
关键词：
tanshinone IIA; transforming growth factor-beta 1; atrial fibroblast; differentiation; ASPARTYL-LYSYL-PROLINE; CARDIAC FIBROBLASTS; TGF-BETA; OXIDATIVE STRESS; CARDIOMYOCYTE HYPERTROPHY; COLLAGEN-SYNTHESIS; HYPERTENSIVE-RATS; HEART-FAILURE; FIBRILLATION; ANGIOTENSIN;
D O I：
10.3892/ijmm.2015.2087
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
The differentiation of atrial fibroblasts into myofibroblasts is a critical event in atrial fibrosis. One of the most important factors in atrial fibroblast differentiation is transforming growth factor-beta 1 (TGF-beta 1). Accumulating evidence indicates that sodium tanshinone IIA sulfonate (STS) possesses antifibrotic properties. In this study, we therefore investigated whether STS attenuates the TGF-beta 1-induced differentiation of atrial fibroblasts. TGF-beta 1 enhanced collagen production, collagen synthesis and the expression of collagen type I and III, as shown by hydroxyproline assay, collagen synthesis assay and western blot analysis, respectively. In addition, as shown by immunohistochemistry and western blot analysis, TGF-beta 1 enhanced the expression of alpha-smooth muscle actin (alpha-SMA), which is the hallmark of myofibroblast differentiation. These responses were attenuated by treatment with STS. In addition, STS suppressed the TGF-beta 1-induced expression of phosphorylated (p) Smad/pSmad3 expression and nuclear translocation. Furthermore, STS supressed extracellular signal-regulated kinase (ERK) phosphorylation. In conclusion, the current study demonstrates that STS exerts antifibrotic effects by modulating atrial fibroblast differentiation through ERK phosphorylation and the Smad pathway.
引用
收藏
页码：1026 / 1032
页数：7
相关论文
共 54 条
[1]   Functional structure and composition of the extracellular matrix [J].
Bosman, FT ;
Stamenkovic, I .
JOURNAL OF PATHOLOGY, 2003, 200 (04) :423-428
[2]   Myocardial fibrosis in transforming growth factor β1 heterozygous mice [J].
Brooks, WW ;
Conrad, CH .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2000, 32 (02) :187-195
[3]   The cardiac fibroblast: Therapeutic target in myocardial remodeling and failure [J].
Brown, RD ;
Ambler, SK ;
Mitchell, MD ;
Long, CS .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2005, 45 :657-687
[4]   Differential behaviors of atrial versus ventricular fibroblasts - A potential role for platelet-derived growth factor in atrial-ventricular remodeling differences [J].
Burstein, Brett ;
Libby, Eric ;
Calderone, Angelino ;
Nattel, Stanley .
CIRCULATION, 2008, 117 (13) :1630-1641
[5]   Fluorofenidone inhibits transforming growth factor-β1-induced cardiac myofibroblast differentiation [J].
Chen, Ling-Xi ;
Yang, Kan ;
Sun, Ming ;
Chen, Qiong ;
Wang, Zhao-He ;
Hu, Gao-Yun ;
Tao, Li-Jian .
PHARMAZIE, 2012, 67 (05) :452-456
[6]   RETRACTED: Hypoxia Preconditioned Mesenchymal Stem Cells Prevent Cardiac Fibroblast Activation and Collagen Production via Leptin (Retracted Article) [J].
Chen, Panpan ;
Wu, Rongrong ;
Zhu, Wei ;
Jiang, Zhi ;
Xu, Yinchuan ;
Chen, Han ;
Zhang, Zhaocai ;
Chen, Huiqiang ;
Zhang, Ling ;
Yu, Hong ;
Wang, Jian'an ;
Hu, Xinyang .
PLOS ONE, 2014, 9 (08)
[7]   NAD(P)H oxidase 4 mediates transforming growth factor-β1-induced differentiation of cardiac fibroblasts into myofibroblasts [J].
Cucoranu, I ;
Clempus, R ;
Dikalova, A ;
Phelan, PJ ;
Ariyan, S ;
Dikalov, S ;
Sorescu, D .
CIRCULATION RESEARCH, 2005, 97 (09) :900-907
[8]   Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases [J].
de Caestecker, MP ;
Parks, WT ;
Frank, CJ ;
Castagnino, P ;
Bottaro, DP ;
Roberts, AB ;
Lechleider, RJ .
GENES & DEVELOPMENT, 1998, 12 (11) :1587-1592
[9]   Transforming growth factor (TGF)-β signaling in cardiac remodeling [J].
Dobaczewski, Marcin ;
Chen, Wei ;
Frangogiannis, Nikolaos G. .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2011, 51 (04) :600-606
[10]   Inflammatory pathways underlying atrial fibrillation [J].
Friedrichs, Kai ;
Klinke, Anna ;
Baldus, Stephan .
TRENDS IN MOLECULAR MEDICINE, 2011, 17 (10) :556-563
123456