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Hypoxia Suppresses TGF-B1-Induced Cardiac Myocyte Myofibroblast Transformation by Inhibiting Smad2/3 and Rhoa Signaling Pathways
被引：15
|作者：
Yan, Zhankui
[1
,2
]
Shen, Daifei
[1
]
Liao, Jilin
[1
,2
]
Zhang, Yanmei
[1
]
Chen, Yicun
[1
]
Shi, Ganggang
[1
]
Gao, Fenfei
[1
]
机构：
[1] Shantou Univ Med Coll, Dept Pharmacol, 22 Xinling Rd, Shantou 515041, Guangdong, Peoples R China
[2] Shantou Univ Med Coll, Dept Pharm, Affiliated Hosp 2, Shantou, Guangdong, Peoples R China
基金：
中国国家自然科学基金;
关键词：
Hypoxia;
TGF-beta;
1;
Cardiac myocyte;
Transformation;
GROWTH-FACTOR-BETA;
TGF-BETA;
MESENCHYMAL TRANSITION;
FIBROBLAST ACTIVATION;
EXTRACELLULAR-MATRIX;
MOLECULAR-MECHANISMS;
DNA-SYNTHESIS;
E2A PROTEINS;
EXPRESSION;
FIBROSIS;
D O I：
10.1159/000486771
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ;
090102 ;
摘要：
Background/Aims: Hypoxia modulation of transforming growth factor (TGF)-beta-induced signaling during myofibroblast transformation is dependent on the specific cell type. The purpose of this study was to explore the effects of hypoxia on myofibroblast transformation of TGF-beta 1-induced cardiomyocyte H9c2 cells. Methods: H9c2 cells were cultured for intermittent hypoxia treatment and TGF-beta 1 treatment. alpha-Smooth muscle actin (alpha-SMA) expression was examined by western blotting and immunofluorescence after treatment. To further explore the possible mechanism for this effect, the effects of hypoxia on three early TGF-beta-dependent signaling pathways, i.e. the Smad2/3, RhoA and mitogen-activated protein kinase (MAPK) pathways, were screened by western blotting. Results: Intermittent hypoxia induced TGF-beta 1 expression, but had no effect on alpha-SMA expression. Exogenous TGF-beta 1 alone upregulated alpha-SMA expression in H9c2 cells in a concentration-and time-dependent manner. alpha-SMA expression declined with the duration of hypoxia after intermittent hypoxia and exogenous TGF-beta 1 cotreatment. Phospho-JNK and phospho-p38 levels were not significantly altered after TGF-beta 1 and hypoxia treatment. However, levels of phospho-ERK increased after TGF-beta 1 treatment and continued to increase after hypoxia co-treatment. The activation of phospho-Smad2/3 and phospho-RhoA induced by TGF beta 1 was significantly reduced after hypoxia co-treatment. Conclusion: Hypoxia can inhibit TGF-beta 1-induced H9c2 myofibroblast transformation, based on inhibition of alpha-SMA expression by suppressing signaling downstream of TGF-beta 1, Smad2/3 and RhoA. It suggested that TGF-beta-mediated cardiomyocyte transformation is not involved in hypoxia-mediated fibrosis. (C) 2018 The Author(s) Published by S. Karger AG, Basel
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页码：250 / 257
页数：8
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