摘要
TGF-β信号显示参与心肌重塑,但具体作用和机制仍不完全清楚。在这项研究中,我们产生的心肌细胞特异性TGF-β 2型受体(TβR2)基因敲除小鼠的功能研究在心肌肥大的TGF-β信号。虽然突变小鼠显示没有明显的生理异常,但是他们导致了严重心肌肥大对异丙肾上腺素(ISO)刺激的小鼠做出反应相较于控制小鼠。P-Smad2的表达明显降低,而磷酸-细胞外信号调节激酶的浓度在突变小鼠的心脏增大。此外,我们还发现,心肌细胞特异性Smad2基因敲除小鼠没有表现出如TβR2基因敲除小鼠中观察到的心脏细胞表型,而MEK-1-调停的丝分裂激活蛋白激酶使用PD98059抑制部分恢复TβR2表型的删除心肌细胞,表明激活TGF-ββ非经典的信号可能有助于心脏表型的TβR2基因敲除小鼠观察。因此,我们的数据最先提供了在体内的遗传证据表明,TβR2可以作为心肌肥大受肾上腺素能刺激抗增生因子,提示不同应力刺激下TβR2在心肌肥大的的复杂角色。
关键词: TβR2;条件基因敲除小鼠;心肌肥厚;异丙肾上腺素;Smad2;细胞外信号调节激酶。
Current Molecular Medicine
Title:Cardiomyocyte-Specific TβR2 Knockout Mice are More Susceptible to Cardiac Hypertrophy Induced by Adrenergic Agonist Stimulation
Volume: 16 Issue: 5
Author(s): X. Fan, L. Liu, Z. Li, X. Peng, Z. Jiang, Y. Guan, X. Wu, X. Yang, J. Wang
Affiliation:
关键词: TβR2;条件基因敲除小鼠;心肌肥厚;异丙肾上腺素;Smad2;细胞外信号调节激酶。
摘要: TGF-β signaling is shown to be involved in cardiac remodeling, but the detailed function and underlying mechanism are still incompletely understood. In this study, we generated cardiomyocyte-specific TGF-β type 2 receptor (TβR2) knockout mice to study the function of TGF-β signaling in cardiac hypertrophy. Although the mutant mice displayed no obvious physiological abnormality, they developed severer cardiac hypertrophy in response to isoproterenol (ISO) stimulation than control mice did. The expression of p-Smad2 was markedly reduced, while the concentration of p-ERK was increased in the hearts of mutant mice. In addition, we also found that cardiomyocyte-specific Smad2 knockout mice did not demonstrate cardiac phenotype as observed on TβR2 knockout mice, while inhibition of MEK-1-mediated activation of MAPK using PD98059 partially rescued the phenotype of TβR2-deleted cardiomyocytes, indicating that activation of TGF-β noncanonical signaling might contribute to cardiac phenotype observed in TβR2 knockout mice. Thus, our data provided the first in vivo genetic evidence to show that TβR2 may function as an anti-hypertrophic factor of cardiac hypertrophy subjected to adrenergic stimulation, suggesting the complex role of TβR2 in cardiac hypertrophy under stimulation of different stresses.
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Cite this article as:
X. Fan, L. Liu, Z. Li, X. Peng, Z. Jiang, Y. Guan, X. Wu, X. Yang, J. Wang , Cardiomyocyte-Specific TβR2 Knockout Mice are More Susceptible to Cardiac Hypertrophy Induced by Adrenergic Agonist Stimulation, Current Molecular Medicine 2016; 16 (5) . https://dx.doi.org/10.2174/1566524016666160429121143
DOI https://dx.doi.org/10.2174/1566524016666160429121143 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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